Boli cromosomale (sindrom down, Klinefelter)

Boli cromosomale

sindrom down

Antenatal screening for Down Symdrome

Antenatal screening of pregnant women aims to identify pregnancies where the risk of fetal chromosomal abnormality is increased above a certain level. This allows women whose babies are identified as having an increased risk of DS the option of prenatal diagnosis. Where requested, prenatal diagnosis is intended to facilitate informed parental choice about pregnancies affected by Down's. Screening may take place in the first or second trimester of pregnancy, and uses maternal age in combination with serum testing, with or without ultrasound scanning, to predict risk.

The first trimester serum test measures levels of pregnancy-associated plasmaprotein-A (PAPP-A) in the maternal blood. The second trimester serum test measures levels of a further four markers in the maternal blood: alpha-fetoprotein (AFP), free -human chorionic gonadotrophin (-hCG), unconjugated oestriol (uE3) and inhibin-A (inhibin). In pregnancies where the foetus has Down's syndrome, PAPP-A, AFP and uE3 levels tend to be low, and inhibin and free -hCG levels tend to be raised. Where levels of all four markers are measured, the second trimester serum test is referred to as the quadruple test; alternatively, double or triple tests (for only two or three of the markers) may be performed, but they are less sensitive.

Fetal ultrasound scanning in the first trimester can indicate an increased risk of DS where features suggestive (but not diagnostic) of DS are identified. The best established of these features is a thickened nuchal fold at the back of the neck, referred to as nuchal translucency (NT). Ultrasound has been reported to increase the efficacy of risk assessment when combined with other screening results, although the time allowed for the process and the skill of the sonographer can affect accuracy.

The most accurate predictions of risk are produced by a two-stage integrated test, which combines the results of full first and second trimester screening. Current research aims to improve the sensitivity (detection rate) and specificity (false-positive rate) of screening. The optimal results for the DS integrated test at present are a detection rate of 85% with a false-positive rate of 1.2% where NT is also measured, and a false-positive rate of 2.7% where NT is not measured. The corresponding false positive rates for a detection rate of 85% fall to 1.8% and 4.2% if the triple test replaces the quadruple test, and to 2.4% and 5.1% if the double test is used.

Current NHS Down's syndrome screening provision in the UK varies between different regions. Private sector screening services are also available.

Fetal RNA (of placental origin) can be detected in maternal plasma during the first trimester, and recent work has suggested that new chromosome 21 markers could be developed for antenatal Down's syndrome screening.

2. Klinefelter

Lab Studies:

Cytogenetic studies

Between 80% and 90% of patients have 47,XXY.

About 10% of patients have mosaicism; karyotypes include 46,XY/47,XXY, 46,XY/48,XXXY, and 47,XXY/48,XXXY.

Remaining cases represent variants such as the 48,XXYY, 48,XXXY, 49,XXXYY, and 49,XXXXY karyotypes.

About 1% of cases are due to a structurally abnormal X in addition to a normal X and Y, such as 47,X,i(Xq)Y and 47,X,del(X)Y.

Hormone testing

High plasma FSH, luteinizing hormone (LH), and estradiol levels and low plasma testosterone have developed in patients aged 12-14 years.

The increase in testosterone in response to administration of human chorionic gonadotropin (hCG) is subnormal.

Urinary gonadotropins are increased due to abnormal Leydig cell function.

Serum osteocalcin levels are decreased and the hydroxyl-proline/creatinine ratio increased, reflecting decreased bone formation and increased bone resorption.

Imaging Studies:

Echocardiography is performed to detect mitral valve prolapse.

Radiographs are performed to detect lower bone mineral density, radioulnar synostosis, and taurodontism.

Histologic Findings: Findings may include small, firm testes with seminiferous tubular hyalinization, sclerosis, and atrophy with focal hyperplasia of mostly degenerated Leydig cells. Germ cells are markedly deficient or absent. Spermatogenesis is demonstrated rarely. In patients with mosaicism, progressive degeneration and hyalinization of seminiferous tubules take place after puberty despite presence of normal-sized testes and spermatogenesis at puberty. Histology of gynecomastic breasts shows hyperplasia of interductal tissue.

Medical Care:

Early identification and anticipatory guidance are extremely helpful (although the syndrome rarely is diagnosed in prepubertal males).

Treatment should address 3 major facets of the disease: hypogonadism, gynecomastia, and psychosocial problems.

Androgen therapy is the most important aspect of treatment. Testosterone replacement should begin at puberty to correct androgen deficiency, provide appropriate virilization, and improve psychosocial status. Regular testosterone injections can promote strength and facial hair growth; build a more muscular body type; increase sexual desire; enlarge size of testes; improve mood, self-image, and behavior; and protect against precocious osteoporosis.

A multidisciplinary team approach will help speech impairments, academic difficulties, and other psychosocial and behavioral problems.

Genetic counseling

The recurrence risk is not increased above that of the general population.

Physicians should provide parents with information from unbiased follow-up studies of children with Klinefelter syndrome.

The best time to reveal the condition to an affected male is probably mid-to-late adolescence when he is old enough to understand his condition.

Surgical Care: Mastectomy may be indicated for gynecomastia. Gynecomastia places considerable psychological strain on the patient and increases risk of breast cancer.

Consultations: Consultations should be sought with a clinical geneticist, endocrinologist, surgeon, psychologist, and speech therapist.

Diet: No special diet is needed.

Activity: No activity restrictions are required.

MEDICATION Section 7 of 11

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography

Drug Category: Androgen -- Exogenous androgen (testosterone) is the treatment of choice for many aspects of Klinefelter syndrome.

Drug Name

Testosterone enanthate (Delatestryl) or cypionate (Depo-Testosterone) -- Major therapeutic aims are to reduce serum gonadotropin concentrations to the upper limits of normal and to induce virilization gradually.

Adult Dose 200 mg IM q2-3wk

Pediatric Dose Beginning at 11-12 years: 50 mg IM every mo; increase dosage yearly in accord with the patient's state of well-being, degree of virilization, growth, and serum gonadotropin concentrations; eventually reaching adult dose

Contraindications Documented hypersensitivity; severe renal, hepatic, or cardiac disease; prostate or breast cancer in males; hypercalcemia

Interactions Increases effects of warfarin; increases propranolol clearance

Pregnancy  X - Contraindicated in pregnancy

Precautions Initiation of therapy may be associated with priapism (rare); other adverse effects include salt and water retention with edema and hypertension, polycythemia, and transient or increased gynecomastia; large doses in older patients may produce prostatic hypertrophy leading to acute bladder outlet obstruction

FOLLOW-UP Section 8 of 11

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography

Further Inpatient Care:

Admission for supportive care is not necessary.

Further Outpatient Care:

The patient should be monitored by an endocrinologist for testosterone replacement therapy.

In/Out Patient Meds:

Administer regular testosterone injections.

3. Cri du chat

Lab Studies:

Conventional cytogenetic studies: The size of the 5p deletion may vary from the entire short arm to only 5p15. A small deletion of 5p may be missed by a conventional cytogenetic technique.

High-resolution cytogenetic studies: Look for a small deletion of 5p.

Fluorescence in situ hybridization

Molecular cytogenetic studies using fluorescent in situ hybridization (FISH) allow the diagnosis to be made in patients with very small deletions. FISH uses genetic markers that have been precisely localized to the area of interest.

The absence of a fluorescent signal from either the maternal or paternal chromosome 5p regions is indicative of monosomy for that chromosomal region.

Chromosome CGH

Chromosome CGH is capable of screening the entire genome for DNA copy-number alterations in a single hybridization.

Its resolution is limited to approximately 5-10 Mb.

The results cannot be mapped directly onto the genome sequence.

Microarray CGH

Microarray CGH uses array elements made from large-insert genomic clones, such as BACS and PACS.

This method has sufficient measurement precision to permit reliable detection of single-copy aberrations affecting individual clones.

Imaging Studies:

Skeletal radiography

Microcephaly, retromicrognathia

Cranial base malformations (reduced cranial base angle and malformed sella turcica and clivus)

Disproportionately short third, fourth, and fifth metacarpals and disproportionately long second, third, fourth, and fifth proximal phalanges (frequent)

Magnetic resonance imaging

Atrophy of the brainstem, atrophic middle cerebellar peduncles and cerebellar white matter

Possible hypoplasia of cerebellar vermis with enlargement of the cisterna magna and fourth ventricle

Echocardiography - To rule out structural cardiac malformations

Other Tests:

Swallowing study for feeding difficulty

Comprehensive evaluation for receptive and expressive language (Most children have better receptive language than expressive language.)

Developmental testing, referral to early intervention, and appropriate school placement

Procedures:

Gastrostomy in infancy to protect airway of patients with major feeding difficulties

Medical Care:

Care is supportive. No treatment exists for the underlying disorder.

Genetic counseling

Female patients are fertile and can deliver viable affected offspring, with an estimated recurrence risk of 50%.

Recurrence risk for a de novo case is 1% or less. Rare recurrences in chromosomally normal parents are most likely the result of gonadal mosaicism for the 5p deletion in one of the parents.

If a parent is a balanced carrier of a structural rearrangement, the risk is substantially high. Risk should be assessed based on the type of structural rearrangement and its pattern of segregation.

Chronic medical problems such as upper respiratory tract infections, otitis media, and severe constipation require appropriate treatment.

Use the relatively good receptive skills to encourage language and communicative development rather than relying on traditional verbal methods.

Early stimulation and introduction to sign language are effective means of developing communication skills (50% of children are able to use sign language to communicate).

Behavior modification programs may be successful in managing hyperactivity, short attention span, low threshold for frustration, and self-stimulatory behaviors (eg, head-banging, hand-waving).

Surgical Care:

Correction of congenital heart defects may be indicated. Medical problems involving minor malformations such as strabismus and clubfoot may be amenable to surgical corrections. Orchiopexy may be necessary for undescended testes.

Issues important to anesthetic plan

Anatomical abnormalities of the airway

Congenital heart disease

Hypotonia

Mental retardation

Temperature maintenance

Consultations:

Clinical geneticist

Developmental pediatrician

Neurologist

Cardiologist

Ophthalmologist

Dentist

Orthopedist

Psychologist

Physical and occupational therapist

Speech language pathologist

Audiologist

Urologist

Diet: No special diet is required.

Activity: Activities are limited because of profound mental retardation and physical handicaps.

4. Sindrom Turner

Lab Studies:

Diagnosis

A karyotype is required for diagnosis. Diagnosis is confirmed by the presence of a 45 X cell line or a cell line with deletion of the short arm of the X chromosome (Xp deletion).

The buccal smear for Barr bodies is obsolete.

Y chromosome

Patients with 45, X/46, XY mosaicism may have mixed gonadal dysgenesis and are at a high risk for gonadoblastoma. These patients may require a prophylactic gonadectomy to prevent death from malignancy.

Patients with ring chromosomes or fragments of chromosomes should be examined for Y chromosomal material for the same reason.

Gonadotrophins

Both LH and FSH may be elevated in untreated patients younger than 4 years. Gonadotropins are later suppressed to normal or near-normal levels, only to rise to menopausal levels after 10 years of age.

Obtain both LH and FSH levels prior to initiating estrogen replacement therapy.

Thyroid function tests

Because of the high prevalence of hypothyroidism in Turner syndrome, obtain thyroid function tests at diagnosis.

Thyroid-stimulating hormone (TSH) measurements should be repeated every 1-2 years or if symptomatic because patients may develop hypothyroidism at a later age.

Glucose metabolism

Abnormalities of glucose metabolism, including overt diabetes mellitus, are more common than in unaffected children.

Glucose tolerance tests should not be done, and obesity should be avoided.

Screening for diabetes mellitus is best performed by obtaining fasting glucose levels.

Urinalysis for glucose should be performed at each follow-up visit with patients taking oxandrolone or human growth hormone.

Continuing care: As routine health maintenance, patients with Turner syndrome should have a blood urea nitrogen (BUN), creatinine, fasting blood sugar (FBS), fasting lipids, liver enzymes, free thyroxine (T4), and TSH measured annually after childhood.

Virilization: Signs of excess androgens are generally absent. If virilization occurs, a search for Y chromosomal material by fluorescent in situ hybridization (FISH) or polymerase chain reaction (PCR) is necessary as part of an evaluation for possible gonadoblastoma.

Imaging Studies:

Renal

At diagnosis, perform an ultrasound evaluation of the kidneys and renal collecting system.

Annual urine culture, BUN, and creatinine are recommended for those patients with abnormalities of the renal collecting system that predispose to obstruction.

Cardiovascular

Perform either echocardiography or MRI examination of the heart at diagnosis. Evaluate 4-limb blood pressures secondary to the high incidence of coarctation of the aorta.

A cardiologist should monitor abnormalities.

Because of the risk of aortic dissection, cardiovascular examinations should be repeated every 5 years during adulthood and prior to assisted reproduction.

A complete cardiovascular evaluation should be completed prior to attempting assisted reproduction.

Bone age

Bone age usually is normal prior to adolescence but is delayed afterward because of the lack of estrogens.

Obtain bone age before starting growth hormone or estrogen therapy. Growth hormone is ineffective if the epiphyses are fused.

Bone density

Osteoporosis is common, but it may be overdiagnosed in short individuals.

Measure bone density initially in adults and 3 years later.

Other Tests:

Audiology

Infants diagnosed at birth should have a hearing assessment in the nursery. Otherwise, formal hearing assessment is recommended at age 1 year and before entering school.

More frequent testing is needed in children with repeated otitis media.

Adults also should have a hearing evaluation at least once with further testing later if hearing loss is suspected.

Medical Care:

Turner syndrome is a lifelong condition. Most people live long and healthy lives, yet some are susceptible to a number of chronic conditions.

Health supervision involves careful medical follow-up care, which includes screening for commonly associated chronic diseases. Early preventive care and treatment also are essential.

In childhood, growth hormone therapy is standard to prevent short stature as an adult. Estrogen replacement therapy usually is required, but starting too early can compromise adult height. Estrogen usually is started from age 12-15 years.

Surgical Care:

Patients have a high risk of keloid formation. This must be taken into consideration if cosmetic surgery is contemplated because keloids may negate any gain from such procedures.

SBE prophylaxis is required prior to any dental or surgical procedure in women with cardiac valve disease to prevent SBE.

Consultations:

Endocrinology

During childhood and adolescence, patients should visit a pediatric endocrinologist at regular intervals.

Attention should be paid to growth and development, thyroid status, and osteoporosis prevention with growth hormone, estrogens, and progestins.

Patients on growth hormone should be seen every 3-4 months.

Cardiology

A cardiologist should evaluate all patients at diagnosis.

Patients found to have significant anomalies should have long-term follow-up care and possibly SBE prophylaxis.

Because of the risks of aortic root dilatation and mortality due to aortic dissection, cardiac evaluation, including echocardiography, may be worthwhile every 5 years, even in patients with normal findings on initial cardiovascular examination.

Patients contemplating pregnancy should have a complete cardiovascular evaluation prior to attempting assisted reproduction or conception.

Nephrology or urology

Almost a third of patients have renal anomalies that may require evaluation and follow-up care by a nephrologist. As a minimum, such patients should have a yearly urine culture, BUN, and creatinine.

Girls with horseshoe kidneys have an increased risk of Wilms tumor. Patients with horseshoe kidneys should have renal ultrasound examinations every 4-6 months until the age of 8 years and every 6-12 months thereafter.

Psychology

Overall psychological health is good, but specific perceptual weaknesses or learning disabilities may be present. Assessment of intelligence, learning ability, motor skills, and social maturity should be made prior to enrollment in kindergarten.

As with any chronic illness, attention should be paid to fostering healthy socialization and to appropriate career and vocational planning.

Genetics

Turner syndrome is not an inherited disorder, and the recurrence risk is low.

Because of infertility, it is rarely passed to offspring.

Consultation is helpful when the condition is diagnosed in utero, or when Turner syndrome is suspected in the setting of a normal peripheral blood karyotype.

Consultation with a geneticist is useful when the patient has known or suspected mosaicism for all, or part, of a Y chromosome. This should be considered when virilization occurs or when there is a small fragment or ring chromosome.

Diet:

Dietary requirements are similar to other children or adults.

Both short stature and ovarian failure are risk factors for osteoporosis, and care should be taken to ensure adequate daily intake of calcium (1.0-1.5 g) and vitamin D (at least 400 IU).

Patients should avoid obesity because it increases already high risks of hypertension and insulin resistance.

Patients with short stature require fewer calories than those of normal height.

Activity: Physical activity should be encouraged as prevention for obesity and osteoporosis.

Drug Category: Human growth hormones -- Primary treatment for short stature. Stimulates growth of linear bone, skeletal muscle, and organs.

Drug Name

Somatotropin (Nutropin, Genotropin, Humatrope, Norditropin, Saizen) -- Taller adult heights are associated with earlier treatment and with the duration of treatment prior to induced or spontaneous puberty. With treatment, approximately 50% of patients reach an adult height of 150 cm (59') or more, compared to an untreated mean adult height of 142 cm (56').

Adult Dose Not recommended at present for adults after the epiphyses have closed

Pediatric Dose Varies with specific product: 0.05 mg/kg/d (as somatropin [Saizen]) SC is one example; individualize according to growth results

Contraindications Documented hypersensitivity; hypersensitivity to benzyl alcohol, cresol, or other preservatives used in preparation of liquid injectable; fused (closed) epiphyses; active neoplasia; neonates

Interactions Corticosteroids interfere with growth-promoting actions; estrogens can cause epiphyseal fusion, which stops growth; patient must be euthyroid for optimal effects

Pregnancy  C - Safety for use during pregnancy has not been established.

Precautions Caution in diabetes mellitus; reconstitute with sterile water for injection if administering to newborns (avoids benzyl alcohol); monitor bone age, thyroid hormones, and blood glucose; intracranial hypertension

Drug Category: Anabolic steroids -- This is an adjuvant for growth hormone therapy.

Drug Name

Oxandrolone (Oxandrin, Anavar) -- Of limited use. Some endocrinologists recommend use in patients diagnosed in their teens to achieve a maximum adult height quickly. When used, it is often combined with growth hormone to allow a lower dose, thus decreasing the potential for adverse effects.

Adult Dose Not recommended

Pediatric Dose <8 years: Not recommended

>8 years: 0.05 mg/kg/d PO; not to exceed 0.05 mg/kg/d

Contraindications Documented hypersensitivity; hypercalcemia

Interactions May worsen glucose tolerance; possible increased sensitivity to PO anticoagulants

Pregnancy  X - Contraindicated in pregnancy

Precautions Caution in heart failure, CAD, edema, hypertension, psychiatric disorders, substance abuse, or liver dysfunction; monitor bone growth and blood glucose

Drug Category: Thyroid replacement therapies -- Used for treatment of hypothyroidism.

Drug Name

Levothyroxine (Synthroid, Levoxyl, Levothroid, L-thyroxine) -- Hypothyroidism is common with Turner syndrome and is treated like any other hypothyroidism. Thyroid hormones influence growth and maturation of tissues. Involved in normal growth, metabolism, and development.

Adult Dose 0.1-0.125 mg/d PO

Pediatric Dose Approximately 3 mcg/kg/d PO

Young children and infants require higher doses per kg; consult package insert or a pediatric endocrinologist; dose should be adjusted to avoid elevated TSH levels and elevated (free) T4 levels

Contraindications Documented hypersensitivity; uncorrected adrenal insufficiency

Interactions Growth hormone ineffective unless euthyroid; cholestyramine may decrease absorption

Pregnancy  A - Safe in pregnancy

Precautions Not for use as treatment in euthyroid obese patients; overtreatment may worsen osteoporosis; caution in cardiovascular disease; monitor thyroid function periodically

Drug Category: Estrogen replacement therapies -- Almost all individuals require estrogen replacement. Usually, this is started at a bone age of 12 years or more because starting earlier may compromise adult height. Estrogens usually are started at a chronologic age of 12-15 years. Adults usually require cyclic therapy with both estrogens and progestins. Transdermal or parenteral estrogens may be useful in limiting some adverse effects of estrogen therapy.

Drug Name

Estrogens -- Available in many forms, eg, ethinyl estradiol (Estinyl), estradiol (Estrace), and conjugated estrogens (Premarin). Restore estrogen levels to concentrations that induce negative feedback at gonadotrophic regulatory centers, which in turn reduces release of gonadotropins from pituitary. Increases synthesis of DNA, RNA, and many proteins in target tissues.

Adult Dose 35-100 PO mcg/d

Pediatric Dose Estrogen should begin at lowest possible dose and not earlier than bone age of 13 y

Some endocrinologists start with a low daily dose of ethinyl estradiol 10 mcg/d or less PO, and cycle therapy after several mo of treatment; low-dose transdermal or parenteral treatment may be preferable and is being investigated 

Contraindications Documented hypersensitivity; breast cancer; undiagnosed abnormal genital bleeding; active thrombophlebitis or thromboembolic disorders; history of thrombophlebitis, thrombosis, or thromboembolic disorders associated with previous estrogen use (except when used in treatment of breast malignancy)

Interactions May reduce hypoprothrombinemic effect of anticoagulants; possible reduced estrogen levels with coadministration of barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes; possible increase in pharmacologic and toxicologic effects of corticosteroids, via inactivation of hepatic P450 enzyme; possible loss of seizure control when administered concurrently with hydantoins

Pregnancy  X - Contraindicated in pregnancy

Precautions May cause some degree of fluid retention and require careful observation; possible undesirable manifestations of excessive estrogenic stimulation

Drug Category: Antihypertensive agents -- These products are used to control hypertension and ultimately prevent complications such as aortic dissection. The two most common class of medications used for these purposes in pediatric patients are beta-blockers and angiotensin-converting enzyme (ACE) inhibitors. Propranolol is an example of one of the beta-blockers used in pediatrics, while captopril is an example of an ACE inhibitor.

Drug Name

Propranolol (Inderal) -- Has membrane-stabilizing activity and decreases automaticity of contractions.

Adult Dose 40-80 mg PO bid initially; increase to 160-320 mg/d (some patients require up to 640 mg/d)

Pediatric Dose 0.5 mg/kg/d PO divided bid/qid; increase gradually q3-7d; dosage range is 2-4 mg/kg/d divided bid

Contraindications Documented hypersensitivity; uncompensated congestive heart failure; bradycardia, cardiogenic shock; AV conduction abnormalities (without pacemaker)

Interactions Coadministration with aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease propranolol effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity of propranolol; toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines may increase with propranolol

Pregnancy  C - Safety for use during pregnancy has not been established.

Precautions Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor closely

Drug Name

Captopril (Capoten) -- Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Adult Dose 12.5-25 mg PO 2-3 times/d; may increase by 12.5-25 mg/dose at 1- to 2-wk intervals up to 50 mg tid

Pediatric Dose 6.25-12.5 mg/dose PO q12-24h; not to exceed 6 mg/kg/d

Contraindications Documented hypersensitivity; renal impairment

Interactions NSAIDs may reduce hypotensive effects of captopril; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases captopril levels; probenecid may increase captopril levels; the hypotensive effects of ACE inhibitors may be enhanced when administered concurrently with diuretics

Pregnancy  C - Safety for use during pregnancy has not been established.

Precautions Category D in second and third trimester of pregnancy; caution in renal impairment, valvular stenosis, or severe congestive heart failure

Drug Category: Vitamins and minerals -- Osteoporosis is common and is a major cause of morbidity in adults. Treatment is the same as for other adult women with osteoporosis. Monitor diet and ensure an intake of at least 1 g/d of calcium and 400 IU/d of vitamin D. Treatment with growth hormone and estrogen also are important in the prevention of osteoporosis later in life.

Drug Name

Ergocalciferol (Calciferol, Drisdol) -- Vitamin D is a micronutrient essential for normal absorption of calcium and phosphorus. It is also produced in response to exposure to ultraviolet B light.

Adult Dose Recommended: 400 IU/d PO

For osteoporosis: 400-1000 IU/d PO or more

Pediatric Dose 400-1000 IU/d PO

Contraindications Documented hypersensitivity; hypercalcemia; malabsorption syndrome

Interactions Cholestyramine, mineral oil, orlistat, and high-fiber diets may decrease absorption; thiazide diuretics may increase effects of vitamin D

Pregnancy  A - Safe in pregnancy

Precautions Pregnancy category C if dose exceeds RDA recommendations; avoid overdosage; efficacy requires adequate intake of calcium; caution in impaired renal function, renal stones, heart disease, or arteriosclerosis

Drug Name

Calcium salts (acetate, carbonate, chloride, gluconate) -- Supplemental source of dietary calcium. Calcium carbonate is 40% elemental calcium.

Adult Dose 1-1.5 g/d elemental calcium PO divided bid/qid

Pediatric Dose Calcium carbonate or other calcium salt: 0.5-1 g/d elemental calcium PO divided bid/qid or 45-65 mg/kg/d PO

Contraindications Renal calculi; hypercalcemia; hypophosphatemia; renal or cardiac disease; digitalis toxicity

Interactions May decrease effects of bisphosphonates, tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones; thiazide diuretics may increase toxicity due to decreased calcium clearance; large intakes of dietary fiber may decrease calcium absorption and levels

Pregnancy  B - Usually safe but benefits must outweigh the risks.

Precautions Hypercalcemia or hypercalcuria may occur when therapeutic amounts are given

Poliosoarticulare

1. Diastrophic Dysplasia

Diastrophic dysplasia was first characterized by Maroteaux and Lamy in 1960. Prior to this, patients with diastrophic dysplasia were described as having 'achondroplasia with clubfoot' or 'arthrogryposis multiplex congenita' (a condition where a person has multiple joint contractures).

Physical features present at birth include short-limbed dwarfism, hitchhiker thumb, and clubfeet. Abnormalities of the palate such as cleft palate or submucous cleft occur in 50% of patients. The ears swell in the first days to weeks of life in 80% of individuals which then subsides spontaneously. Later, the ears have a 'cauliflower' appearance. Fingers are short and broad with ulnar deviation. The thumb has a hitch-hiker type appearance. There is increased mortality in infancy due to respiratory complications but thereafter, people with diastrophic dysplasia have a normal life span.

Orthopedic problems are common. The joints can be dislocated, especially the shoulder, elbows, hips, and patellae (knee caps). Flexion contractures of knees and shoulders are common. Scoliosis is not present at birth but often is progressive, especially in the early teens. Treatment of the scoliosis includes bracing and occasionally, spinal fusion. Progressive cervical kyphosis can also occur with subluxation of the cervical spine which can result in spinal cord compression.

The average length at birth is 42cms. Horton et. al. in 1982 published a growth curve of individuals with diastrophic dysplasia. The average adult height is 118cms with males ranging from 86-127cms and females ranging from 104-122cms. Final height is influenced by the presence of scoliosis, hip and knee contractures, and foot deformities.

Diastrophic dysplasia is inherited as an autosomal recessive condition (see genetics section for further details). This means that average-sized parents have a one in four (or 25%) chance of having additional children with diastrophic dysplasia. Diastrophic dysplasia occurs at very low frequency in most populations but is seen frequently in Finland. The gene for diastrophic dysplasia has been found and is called 'diastrophic dysplasia sulfate transporter' (DTDST). Prenatal diagnosis has been performed using ultrasound and by molecular DNA diagnosis.

maladia aminiotica - amniocenteza

sindactilie, polidactilie -

Karyotyping is a test to identify chromosome abnormalities as the cause of malformation or disease. This test can:

Count the number of chromosomes

Look for structural changes in chromosomes

The results may indicate genetic changes linked to a disease.

The blood test is usually performed to evaluate a couple with a history of miscarriages or to evaluate an abnormal appearance of the body that suggests a genetic abnormality. The bone marrow or blood test can be done to identify the Philadelphia chromosome that is present in 85% of those with Chronic myelogenous leukemia (CML). The amniotic fluid test is done to evaluate a developing fetus for chromosome abnormalities.

cheiloschisis ( cleft lip ) + palatoschisis - nu exista markeri biochimici

cheilognata - nu o gasesc - e posibil sa nu fi scris eu corect

Sistem respirator

hernie diafragmatica longitudinala

The pregnant mother may have shown signs of polyhydramnios (excessive amounts of amniotic fluid). Fetal ultrasound may show abdominal contents in the chest cavity.

Examination of the infant shows:

chest movements asymmetric with breathing

breath sounds absent on the affected side

bowel sounds heard in the chest

concave abdomen that feels less full on examination by touch (palpation)

A chest X-ray may show abdominal organs in chest cavity.

After birth, your baby's physician will perform a physical examination. A chest x-ray is done to look at the abnormalities of the lungs, diaphragm, and intestine. A blood test known as an arterial blood gas is often performed to evaluate the baby's breathing ability.

Other tests that may be performed include:

blood test for chromosomes (to determine if there is a genetic problem)

ultrasound of the heart (echocardiogram)

atrezie coanala - nu sunt analize specifice, diag. se bazeaza pe examinare fizica

maladia pierre robin - nu sunt analize specifice, diag. se bazeaza pe examinare fizica

Sistem cardiovascular

DSA - defect septal atrial

How is an atrial septal defect diagnosed?

Your child's physician may have heard a heart murmur during a physical examination, and referred your child to a pediatric cardiologist for a diagnosis. A heart murmur is simply a noise caused by the turbulence of blood flowing through the opening from the left side of the heart to the right.

A pediatric cardiologist specializes in the diagnosis and medical management of congenital heart defects, as well as heart problems that may develop later in childhood. The cardiologist will perform a physical examination, listening to the heart and lungs, and make other observations that help in the diagnosis. The location within the chest that the murmur is heard best, as well as the loudness and quality of the murmur (harsh, blowing, etc.) will give the cardiologist an initial idea of which heart problem your child may have. Other tests are needed to help with the diagnosis, and may include the following:

Chest X-ray - A diagnostic test that uses invisible electromagnetic energy beams to produce images of internal tissues, bones and organs onto film. With an ASD, the heart may be enlarged because the right atrium and ventricle have to handle larger amounts of blood flow than normal. Also, there may be changes that take place in the lungs due to extra blood flow that can be seen on an X-ray.

Electrocardiogram (ECG or EKG) - A test that records the electrical activity of the heart, shows abnormal rhythms (arrhythmias or dysrhythmias) and detects heart muscle stress.

Echocardiogram (echo) - A procedure that evaluates the structure and function of the heart by using sound waves, recorded on an electronic sensor, that produce a moving picture of the heart and heart valves. An echo can show the pattern of blood flow through the septal opening and determine how large the opening is, as well as how much blood is passing through it.

Cardiac Catheterization - A procedure that gives very detailed information about the structures inside the heart. Under sedation, a small, thin, flexible tube (catheter) is inserted into a blood vessel in the groin and guided to the inside of the heart. Blood pressure and oxygen measurements are taken in the four chambers of the heart, as well as in the pulmonary artery and aorta. Contrast dye is injected to more clearly visualize the structures inside the heart. If the echocardiogram has provided enough information, this procedure is often not needed to evaluate ASD.

Cardiac Magnetic Resonance Imaging (MRI) - A non-invasive test that uses three-dimensional imaging technology produced by magnets to accurately determine blood flow and functioning of the heart as it is working.

What are the treatments for atrial septal defect?

Specific treatment for ASD will be determined by your child's physician based on:  

your child's age, overall health and medical history

extent of the disease

your child's tolerance for specific medications, procedures or therapies

how your child's doctor expects the disease to progress

your opinion or preference

Ostium secundum atrial septal defects may close spontaneously as a child grows. Once an atrial septal defect is diagnosed, your child's cardiologist will evaluate your child periodically to see if it is closing on its own. Usually, an ASD will be repaired if it has not closed on its own by the time your child starts school, to prevent lung problems that will develop from long-term exposure to extra blood flow. The decision to close the ASD also may depend on the size of the defect. Treatment may include:

Medical Management -- Many children have no symptoms and require no medications, however some children may need to take medications to help the heart work better, since the right side is under strain from the extra blood passing through the ASD. Medication that may be prescribed includes the following:

Digoxin - a medication that helps strengthen the heart muscle, enabling it to pump more efficiently.

Diuretics - the body's water balance can be affected when the heart is not working as well as it could. These medications help the kidneys remove excess fluid from the body.

Infection Control - Children with certain heart defects are at risk for developing an infection of the inner surfaces of the heart known as bacterial endocarditis. A common procedure that puts your child at risk for this infection is a routine dental check-up and teeth cleaning. Other procedures also may increase the risk of heart infection. Bacterial endocarditis often can be prevented by giving children with heart defects an antibiotic by mouth before the procedure. It is important that you inform all medical personnel that your child has an ASD so they may determine if the antibiotics are necessary before a procedure.

Cardiac Catheterization - If the defect is large and your child develops severe symptoms, or the defect seems to be causing injury to the aortic valve, your child's cardiologist may recommend cardiac catheterization treatment or surgery immediately. One recent development allows treatment through cardiac catheterization. A patch shaped like an umbrella is closed (like a closed umbrella) and inserted into the damaged area through a small tube, called a catheter. The umbrella patch is then opened to cover the hole. This method requires a small incision, avoiding the need for open-heart surgery.

Surgical Repair - The surgical closure of an ASD is carried out through an incision in the middle of the chest. A heart-lung machine is used to do the work of the heart while the heart is cooled, stopped, emptied and opened through the right atrium. The hole in the wall between the right and left atrium is closed with stitches if it is small, or, if too large, with a patch of thin leather-like material called pericardium, which makes up the sac covering the heart. The right atrium is then closed and the heart is restarted as the heart-lung machine is withdrawn. Advancements in cardiovascular surgical repair include minimally invasive cardiac surgery.

DSV - defect septal ventricular

Your child's physician may have heard a heart murmur during a physical examination and referred your child to a pediatric cardiologist for a diagnosis. A heart murmur is simply a noise caused by the turbulence of blood flowing through the opening from the left side of the heart to the right.

A pediatric cardiologist specializes in the diagnosis and medical management of congenital heart defects, as well as heart problems that may develop later in childhood. The cardiologist will perform a physical examination, listening to the heart and lungs, and make other observations that help in the diagnosis. The location within the chest where the murmur is heard best, as well as the loudness and quality of the murmur (harsh, blowing, etc.), will give the cardiologist an initial idea of which heart problem your child may have. Other tests are needed to help with the diagnosis, and may include the following:

Chest X-ray - A diagnostic test that uses invisible electromagnetic energy beams to produce images of internal tissues, bones and organs onto film. With a VSD, the heart may be enlarged because the right ventricle handles larger amounts of blood flow than normal. Also, there may be changes that take place in the lungs due to extra blood flow that can be seen on an X-ray.

Electrocardiogram (ECG or EKG) - A test that records the electrical activity of the heart, shows abnormal rhythms (arrhythmias or dysrhythmias) and detects heart muscle stress.

Echocardiogram (echo) - A procedure that evaluates the structure and function of the heart by using sound waves, recorded on an electronic sensor, that produce a moving picture of the heart and heart valves. An echo can show the pattern of blood flow through the septal opening and determine how large the opening is, as well as how much blood is passing through it.

Cardiac Catheterization - A procedure that gives very detailed information about the structures inside the heart. Under sedation, a small, thin, flexible tube (catheter) is inserted into a blood vessel in the groin and guided to the inside of the heart. Blood pressure and oxygen measurements are taken in the four chambers of the heart, as well as in the pulmonary artery and aorta. Contrast dye also is injected to more clearly visualize the structures inside the heart.

Cardiac Magnetic Resonance Imaging (MRI) - A non-invasive test that uses three-dimensional imaging technology produced by magnets to accurately determine blood flow and functioning of the heart as it is working.

What are the treatments for ventricular septal defect?

Specific treatment for VSD will be determined by your child's physician based on:  

your child's age, overall health and medical history

extent of the disease

your child's tolerance for specific medications, procedures or therapies

how your child's doctor expects the disease may progress

your opinion or preference

Small ventricular septal defects may close spontaneously as your child grows. A larger VSD usually requires surgical repair. Regardless of the type, once a ventricular septal defect is diagnosed, your child's cardiologist will evaluate your child periodically to see whether it is closing on its own. A VSD will be repaired if it has not closed on its own -- to prevent lung problems that will develop from long-time exposure to extra blood flow. Treatment may include:

Medical Management - Some children have no symptoms and require no medication. Most children, however, may need to take medications to help the heart work better, since the right side is under strain from the extra blood passing through the VSD. Medications that may be prescribed include the following:

Digoxin -- A medication that helps strengthen the heart muscle, enabling it to pump more efficiently.

Diuretics -- The body's water balance can be affected when the heart is not working as well as it could. These medications help the kidneys remove excess fluid from the body.

Adequate Nutrition - Infants with a larger VSD may become tired when feeding, and are not able to eat enough to gain weight. Options that can be used to ensure your baby will have adequate nutrition include the following:

High-calorie Formula or Breast milk -- Special nutritional supplements may be added to formula or pumped breast milk that increase the number of calories in each ounce, thereby allowing your baby to drink less and still consume enough calories to grow properly.

Supplemental Tube Feedings -- Feedings given through a small, flexible tube that passes through the nose, down the esophagus and into the stomach can either supplement or take the place of bottle feedings. Infants who can drink part of their bottle, but not all, may be fed the remainder through the feeding tube. Infants who are too tired to bottle-feed may receive their formula or breast milk through the feeding tube alone.

Infection Control - Children with certain heart defects are at risk for developing an infection of the inner surfaces of the heart known as bacterial endocarditis. A common procedure that puts your child at risk for this infection is a routine dental check-up and teeth cleaning. Other procedures may also increase the risk of the heart infection occurring. Giving children with heart defects an antibiotic by mouth before these procedures can help prevent bacterial endocarditis. It is important that you inform all medical personnel that your child has a VSD so they may determine if the antibiotics are necessary before a procedure.

Cardiac Catheterization - Your child's VSD may be repaired surgically in the operating room or by a cardiac catheterization procedure. One method currently being used to close some VSDs is the use of a device called a septal occluder. During this procedure, the child is sedated and a small, thin, flexible tube is inserted into a blood vessel in the groin and guided into the heart. Once the catheter is in the heart, the cardiologist will pass the septal occluder into the VSD. The septal occluder closes the ventricular septal defect providing a permanent seal.

Surgical Repair - Some types of VSDs will close on their own with time. Many, however, are too large or are positioned such that they cannot close on their own and require surgical closure.

The surgical closure of a VSD is carried out through an incision in the middle of the chest. The breast bone is split in the middle and spread apart to expose the heart. A heart-lung machine is used to do the work of the heart while the heart is cooled, stopped, emptied and opened, usually through the right atrium. The hole in the wall between the right and left ventricles is closed by sewing to it a patch of Dacron cloth or a patch of thin leather-like material called pericardium. The heart is then closed and restarted as the heart-lung machine is withdrawn. Advancements in cardiovascular surgical repair include minimally invasive cardiac surgery.

Fallot 3 si 4 de vase mari - nu am gasit pe net analize biochimice, sunt in cursuri analize pentru mai multe boli de inima

transpozitii ale inimii - - nu am gasit pe net analize biochimice, sunt in cursuri analize pentru mai multe boli de inima

Sistem digestiv

atrezie esofagiana - articol

gastroschizis - articol

omfalocel - articol

Maladia Hischprung (megacolon congenital) - nu am gasit nimic

Atrezie anorectala - nu am gasit nimic

Sistem urinar

sunt testele clasice valabile si pentru nou nascut

boala chistica renala

Early in the course, the physician may identify:

The patient is passing large amounts of diluted urine, with salt wasting

The urine specific gravity is low and fixed

Blood pressure may be low and require salt supplements

The diagnosis can be established with:

Abdominal ultrasound or abdominal CT scan - these may show small kidneys or multiple cysts on the kidneys

Renal biopsy -- this may show tubulo-interstitial nephropathy and medullary cysts.

As the disease progresses, kidney failure follows:

Increasing creatinine levels

Increasing BUN (blood urea nitrogen)

Decreasing creatinine clearance

Elevated blood pressure

Anemia (shown on complete blood count)

Small, shrunken kidneys (shown on ultrasound)

Treatment 

There is no cure for this disease. At first, treatment focuses on controlling symptoms, minimizing complications, and slowing the progression of the disease. Because of the loss of water and salt, the patient will need a liberal intake of both to avoid dehydration.

As the disease progresses, kidney failure develops and appropriate changes will be made:

If high blood pressure develops, anti-hypertensive medications may be needed.

Anemia may require erythopoeitin treatment to build red blood cells.

Diet will be modified to limit phosphorous- and potassium-containing foods.

Once end-stage kidney disease approaches, dialysis may be started. If a suitable donor becomes available, a kidney transplant may be performed. Kidney transplant is the preferred treatment. It has excellent results.

hipospazias - nu am gasit

anomalii de forma si fuziune - articole

Sistem reproducator

intersexualitatea

Lab Studies:

Logical workup in infants with ambiguous genitalia includes the following:

Chromosomal analysis

Endocrine screening

Serum chemistries/electrolyte tests

Androgen-receptor levels

5-alpha reductase type II levels

Imaging Studies:

Renal/bladder ultrasound: Ultrasound can be performed at the bedside in the neonatal ICU. Ultrasound usually allows visualization of a neonate's adrenal glands, which may be enlarged in infants with CAH; however, normal ultrasound findings in the adrenal glands do not exclude a diagnosis of CAH. When adrenal glands are enlarged in patients with CAH, the glands have a cribriform appearance. Ultrasound also helps identify mllerian structures. In a neonate, findings of ambiguous genitalia, enlarged adrenal glands, and evidence of a uterus are virtually pathognomonic for CAH.

Genitography: A genitogram helps determine ductal anatomy. In a neonate with ambiguous genitalia, a catheter can be inserted into the distal urogenital sinus (urethra). Contrast is injected to outline the internal ductal anatomy. Findings may indicate normal urethral anatomy, an enlarged utricle, a mllerian remnant in a male, a common urogenital sinus, or an area of vaginal and urethral confluence in female neonates.

CT scanning and MRI are usually not indicated but may help identify internal anatomy.

Procedures:

Exploratory laparotomy/gonadal biopsy: Open exploration may help identify internal duct anatomy and allow gonadal tissue to be obtained for histologic characterization; however, many authors advocate laparoscopy for this purpose.

Diagnostic laparoscopy/gonadal biopsy: A laparoscope may be inserted just inferior to the umbilicus under general anesthesia, allowing rapid identification and delineation of the internal duct anatomy without the morbidity associated with open exploration. Biopsy of gonads may be performed laparoscopically by placing additional trocars.

Histologic Findings: Histologic analysis of gonadal biopsy specimens may identify ovarian tissue, testicular tissue, ovotestes, or streak gonads.

Medical Care: Medical therapy for intersex conditions depends on the underlying cause and is indicated for the conditions associated with ambiguous genitalia, including CAH. Supplemental hormone therapy may be implemented if gonadal function is compromised.

Surgical Care:

In a virilized female, the surgical procedure is termed feminizing genitoplasty and includes vaginoplasty and clitoroplasty.

Undervirilized males typically have hypospadias requiring surgical reconstruction. Gender reassignment may be considered in patients with male pseudohermaphrodism and genital inadequacy.

SNC

hidrocefalie - articole

spina bifida posterioara

How is spina bifida diagnosed?

Diagnostic tests can be performed during pregnancy to evaluate the fetus for spina bifida. The tests include the following:

blood tests

The American College of Obstetrics and Gynecology (ACOG) recommends that a blood test be offered between 15 to 20 weeks to all women who are pregnant who have not previously had a child with an ONTD and who do not have a family history of ONTD. This blood test measures alpha-fetoprotein (AFP) levels and other biochemical markers in the mother's blood to determine whether her pregnancy is at increased risk for an ONTD. AFP is a protein normally produced by the fetus that crosses the placenta into the mother's blood. Generally, if a fetus has an ONTD, the alpha-fetoprotein level in the mother's blood will be increased. Although this test does not tell for certain whether a fetus has an ONTD, it will determine which pregnancies are at greater risk, so that additional testing may be performed.

prenatal ultrasound (Also called sonography.) - a diagnostic imaging technique which uses high-frequency sound waves and a computer to create images of blood vessels, tissues, and organs. Ultrasounds are used to view internal organs as they function, and to assess blood flow through various vessels. Prenatal ultrasound may be able to detect an ONTD, and may be used to examine other organs and body systems of the fetus.

amniocentesis - a procedure that involves inserting a long, thin needle through the mother's abdomen into the amniotic sac to withdraw a small sample of the amniotic fluid for examination. The fluid is then tested to determine the presence or absence of an open neural tube defect. Small or closed defects may not be picked up by this test.

Management of spina bifida:

The primary goal of managing spina bifida is to prevent infection and to preserve the spinal cord and nerves that are exposed outside of the body. Specific management of spina bifida will be determined by your baby's physician based on:

your baby's gestational age, overall health, and medical history

the extent and type of spina bifida

your baby's tolerance for specific medications, procedures, or therapies

expectations for the course of spina bifida

your opinion or preference

A cesarean delivery is often performed to decrease the risk of damage to the spinal cord that may occur during a vaginal delivery. Babies born with a meningocele or a myelomeningocele usually require care in the neonatal intensive care unit (NICU) for evaluation and for surgery to close the defect. Surgery can help manage the problems, but it can not restore muscle function or sensation to a normal state. Surgical interventions may be needed for the following:

repair and closure of the lesion

treatment of hydrocephalus

orthopaedic problems

Orthopaedic problems may include curvatures in the back, hip dislocations, ankle and foot deformities, and contracted muscles. Babies and children with spina bifida are also very susceptible to breaking their bones since their bones may be weaker than normal.

bowel and bladder problems

Bowel and bladder problems may require surgery to improve function in elimination, for incontinence, constipation, or when the bladder does not empty completely.

Following surgery, you will receive instructions on caring for your baby at home. Education may include the following:

examining the skin, especially over bony areas such as the elbows, buttocks, back of the thighs, heel, and foot areas. Recommendations may include changing your baby's position frequently to prevent skin breakdown and pressure sores.

promoting bowel and bladder function

ways to feed you baby and monitor your baby's nutrition

promoting activity and mobility

encouraging age-appropriate growth and development

Not all babies will require surgical repair of spina bifida. Non-surgical management of spina bifida may include the following:

rehabilitation

positioning aids (used to help the child sit, lie, or stand)

braces and splints (used to prevent deformity, promote support or protection)

medications

Latex precautions:

Babies with spina bifida are at high risk for developing a latex allergy due to exposure to latex from multiple medical and surgical procedures. Precautions are taken by the healthcare team to reduce the baby's exposure to products that contain latex. Your baby's healthcare providers can help you identify products that contain latex and also find products that are latex-free.

Life-long considerations:

Since spina bifida is a life-long condition that is not curable, management often focuses on preventing or minimizing deformities and maximizing the child's capabilities at home and in the community. Positive reinforcement will encourage the child to strengthen his/her self-esteem and promote as much independence as possible.

The full extent of the problem is usually not completely understood immediately after birth, but may be revealed as the child grows and develops.

Future pregnancies:

Genetic counseling may be recommended by your physician to discuss the risk of recurrence in a future pregnancy, as well as vitamin therapy (a prescription for folic acid) that can decrease the recurrence risk for ONTDs. Supplemental folic acid, a B vitamin, if taken one to two months prior to conception and throughout the first trimester of pregnancy, has been found to decrease the reoccurrence of ONTDs for couples who have had a previous child with an ONTD. You cannot obtain the proper amount of folic acid in a multivitamin. A prescription from an obstetrician or other healthcare provider is needed in order to receive the proper dosage.

Hepatologie si moleculare

1. hemangioame

Single-photon emission computed tomography (SPECT)

MRI

CT scan of the liver

Hepatic angiogram

Blood tests (thrombocytopenia may be present in large hemangiomas)

Treatment 

Most cavernous hepatic hemangiomas are treated only if there is persistent pain.

Treatment for infantile hemangioendothelioma depends on the child's growth and development. The following treatments may be needed:

Medications for heart failure

Embolization of the liver

Ligation of the liver artery

Surgery to remove the tumor

2. hemoglobina M (methhemoglobinemia)

Lab Studies:

An arterial blood sample from a patient with methemoglobinemia is characteristically chocolate brown.

Blood that is cyanotic or dark in color due to cardiopulmonary disease turns red on exposure to oxygen, whereas blood with methemoglobin does not.

A quick and easy bedside test is to bubble 100% oxygen in the tube containing the dark blood. If the blood remains dark, it most likely is due to the presence of methemoglobin.

Another simple test is to place 1-2 drops of patient blood on white filter paper, then evaluate for color change upon exposure to oxygen (this test can be accelerated by gently blowing supplemental oxygen onto the filter paper). Deoxygenated hemoglobin changes from dark red/violet to bright red, while methemoglobin remains brown.

Serum methemoglobin levels greater than 1% are considered abnormal, although higher levels are commonly encountered in smokers (and patients with long-term exposure to second-hand smoke). Symptomatic individuals usually have levels greater than 40-50%.

Serum levels of nitrites or other offending drugs may be determined.

NADH reductase levels should be checked.

Hemoglobin electrophoresis may be needed to confirm hemoglobin M disease.

Pulse oximetry may be a useful tool in the cyanotic patient, although its results must be interpreted with caution.

The blood is exposed to light using a small probe placed on a finger or toe. Light at wavelengths of 660 nm and 940 nm are used, and the ratio of absorption of light at each of these wavelengths is converted into oxygen saturation using calibration curves.

A pulse oximetry reading in a child with respiratory or cardiac disease reflects the degree of hypoxia and is proportionate to the amount of reduced hemoglobin.

In a patient with methemoglobinemia, the severity of the cyanosis does not correspond to the pulse oximetry reading. The patient may appear extremely cyanotic but have a pulse oximetry reading in the high 80s.

In methemoglobinemia, the oxygen saturations plateau at around 85%; therefore, a patient with a methemoglobin level of 5% and a patient with a methemoglobin level of 40% both have pulse oximetry readings of around 85%.

Methemoglobin increases absorption of light at both wavelengths (more at 940 nm) and, therefore, offers optical interference to the pulse oximetry by falsely absorbing light. This leads to the plateau in the oxygen saturation at 85%.

Cooximetry should be performed to evaluate for methemoglobinemia (although some equipment does not differentiate between sulfhemoglobin and methemoglobin).

Imaging Studies:

Chest radiography may be helpful to exclude pulmonary or cardiac disease.

TREATMENT Section 6 of 10

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Medical Care: Once the diagnosis of methemoglobinemia has been confirmed, and appropriate treatment initiated, a search for the underlying etiology should be made.

In acquired disease, attempting to identify the toxin or drug may be achieved by performing blood levels and/or gastric lavage. In the asymptomatic patient with a low level of methemoglobin, monitoring serial serum levels is all that may be necessary. The levels normalize over time and after the removal of the offending agent.

If the methemoglobin levels are greater than 30%, methylene blue should be administered IV at 1-2 mg/kg (up to 50 mg/dose in adults, adolescents, and older children) as a 1% solution over 5 minutes; repeat in one hour, if necessary. Methylene blue is an oxidant at levels greater than 7 mg/kg (and therefore may cause methemoglobinemia in susceptible patients), so care must be taken in administration of this drug. Methylene blue is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency because it can lead to severe hemolysis.

Ascorbic acid is an antioxidant that may also be used for methemoglobin levels greater than 30%.

N-acetylcysteine has been shown to reduce methemoglobin in recent studies, but it is not yet an approved treatment for methemoglobinemia.

No pharmaceutical treatment for hereditary forms of methemoglobinemia exists.

Oral ascorbic acid (200-500 mg) has been found to be partially effective if continued on an ongoing basis; however, this therapy has the potential risk of renal stones and hyperoxaluria. Methylene blue has also been used in these patients.

For severe cases, exchange transfusion may be necessary.

Consultations: Consultation with other specialists, such as hematologists, cardiologists, and pulmonologists, may be required to assist in the search for the cause of the methemoglobinemia.

Diet:

Some vegetables, such as beets, spinach, and carrots, are high in nitrite content and may need to be avoided in susceptible patients.

Well water can be contaminated with oxidants and could lead to methemoglobinemia, especially in small infants (<4 mo).

Activity: No change in activity is indicated.

3. siclemia - talasemie - articole

4. sferocitoza ereditara - articole

5. lipsa glc 6 P deh -

Lab Studies:

Measure the actual enzyme activity of G6PD rather than the amount of G-6-PD protein. Performing assays for G-6-PD during hemolysis and reticulocytosis may affect levels and not reflect baseline values.

Obtain a CBC count with reticulocyte count to determine the level of anemia and bone marrow function.

Indirect bilirubinemia occurs with excessive hemoglobin degradation and can produce clinical jaundice.

Serum haptoglobin levels serve as an index of hemolysis and will be decreased.

Imaging Studies:

Abdominal ultrasound may be useful in assessing for splenomegaly and gallstones.

Histologic Findings: Acute hemolysis from G-6-PD deficiency is associated with formation of Heinz bodies, which consist of denatured hemoglobin.

TREATMENT

Medical Care: Identification and discontinuation of the precipitating agent is critical. Individuals are treated with oxygen and bed rest, which may afford symptomatic relief.

Consultations:

Hematologists

Geneticists

Diet: Patients must avoid broad beans (ie, fava beans). Favism occurs only in the Mediterranean variety of G-6-PD deficiency.

Activity: Curtailment of physical activity may be necessary if severe anemia results from hemolysis.

6. fenilcetonurie

Testare fenilalanina din sange

7. alcaptonurie

Urinalysis is positive for reducing substance. Further urine testing shows a positive ferric chloride test.

Lab Studies:

Homogentisic acid can be identified in urine using gas chromatography-mass spectroscopy. Spectrophotometric quantitation shows two orders of magnitude elevations above normal.

Since many patients present without dark urine, looking for homogentisate in all patients with radiographic evidence of osteoarthritis may be advisable.

After DNA extraction from whole blood, screening for mutations can be performed with PCR technique.

Imaging Studies:

Radiographs

A spinal radiograph reveals disk degeneration combined with dense calcification, particularly in the lumbar area.

A chest radiograph is advised to assess for possible involvement of aortic or mitral valves.

In affected individuals over 55, CT scanning may provide evidence of coronary artery calcifications.

Other Tests:

Electrocardiography may be advisable, with particular attention directed at any signs of myocardial insufficiency.

Procedures:

Other studies and procedures should be directed at the joint disease itself. Joint replacements may become necessary in severely affected larger joints.

Histologic Findings: In association with the gross visual finding of black-stained cartilage in various areas of the body (eg, larynx, costochondral junctions, trachea), microscopic examination reveals pigment deposition within and outside cells in these tissues. No specific stain is available to distinguish homogentisate-derived pigment from melanin, and the 2 compounds have very similar solubility characteristics.

TREATMENT

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Medical Care:

In infancy, a history of dark-stained diapers should alert the physician.

Infants, young children, and asymptomatic young adults can be evaluated with simple urine testing on an outpatient basis.

Medical therapy is used to ameliorate the rate of pigment deposition. This minimizes articular and cardiovascular complications in later life.

Reduction of phenylalanine and tyrosine has reportedly reduced homogentisic acid excretion. Whether a mild dietary restriction from early in life would avoid or minimize later complications is not known, but such an approach is reasonable.

Vitamin C, up to 1 g/d, is recommended for older children and adults. The mild antioxidant nature of ascorbic acid helps to retard the process of conversion of homogentisate to the polymeric material that is deposited in cartilaginous tissues.

Limited use of nitisinone, an inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase, which mediates formation of homogentisic acid, has been reported. Urinary homogentisate excretion was markedly reduced, but safety of prolonged use is still an open question.

Surgical Care:

Older individuals may require removal of lumbar discs with fusion.

Hip, shoulder, or knee joint replacement may be necessary.

Consultations:

Biochemical geneticist

Neurosurgeon

Orthopedist

Cardiologist for older individuals

Diet:

Reduction of phenylalanine and tyrosine reportedly reduced homogentisic acid excretion in the urine of a child. In an adult, a similar restriction reportedly had no effect on excretion of the abnormal metabolite. Whether a mild dietary restriction from early in life would avoid or minimize later complications is not known, but such an approach is reasonable.

Vitamin C, up to 1 g/d, is recommended for older children and adults.

8. albinism

It's not always easy to diagnose the exact type of albinism a person has; there are two tests available that can identify only two types of the condition. Recently, a blood test has been developed that can identify carriers of the gene for some types of albinism; a similar test during amniocentesis can diagnose some types of albinism in an unborn child. A chorionic villus sampling test during the fifth week of pregnancy may also reveal some types of albinism.

The specific type of albinism a person has can be determined by taking a good family history and examining the patient and several close relatives.

The 'hairbulb pigmentation test' is used to identify carriers by incubating a piece of the person's hair in a solution of tyrosine, a substance in food which the body uses to make melanin. If the hair turns dark, it means the hair is making melanin (a 'positive' test); light hair means there is no melanin. This test is the source of the names of two types of albinism: 'ty-pos' and 'ty-neg.'

The tyrosinase test is more precise than the hairbulb pigmentation test. It measures the rate at which hair converts tyrosine into another chemical (DOPA), which is then made into pigment. The hair converts tyrosine with the help of a substance called 'tyrosinase.' In some types of albinism, tyrosinase doesn't do its job, and melanin production breaks down.

Treatment

There is no treatment that can replace the lack of melanin that causes the symptoms of albinism. Doctors can only treat, not cure, the eye problems that often accompany the lack of skin color. Glasses are usually needed and can be tinted to ease pain from too much sunlight. There is no cure for involuntary eye movements (nystagmus), and treatments for focusing problems (surgery or contact lenses) are not effective in all cases.

Crossed eyes (strabismus) can be treated during infancy, using eye patches, surgery or medicine injections. Treatment may improve the appearance of the eye, but it can do nothing to cure the underlying condition.

Patients with albinism should avoid excessive exposure to the sun, especially between 10 a.m. and 2 p.m. If exposure can't be avoided, they should use UVA-UVB sunblocks with an SPF of at least 20. Taking beta- carotene may help provide some skin color, although it doesn't protect against sun exposure.

9. mucopolizaharidoze 1-6 - nu am gasit nimic

10. glicogenoze (von gierke, pompe, corey) - articole

11. gangliozidoze(lambe, gaudet, lumampic) - articol