Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital hypothyroidism (CH) is the commonest treatable cause of mental retardation. The prevelance is 1/3000 - 1/4000 live births worldwide. The importance of CH is that, the longer the diagnosis of CH is delayed, the higher the risk of mental retardation and neurologic sequale; such as poor motor coordination, ataxia, spastic diplegia, muscular hypotonia, strabismus, learning disability and diminished attention span. The most common cause of permenant CH is thyroid dysgenesis (85-90%) in which the transcription factors TTF1,TTF2 and PAX8 would appear to be obvious candidate genes in the aetiology. Especially cardiac defects and some other birth defects are described in patients with CH. Inborn errors of thyroid hormonogenesis are responsible for 10-15% of CH cases and usually have autosomal recessive inheritance, consistent with a single gene mutation. Transient CH is very common in prematures with an estimate of 10% of CH babies identified on newborn screening, or 1 in 40,000 neonates. CH neonates are usually symptom-free and the most encountered symptoms are prolonged jaundice, large fontanelles and umbilical hernia. In general, the extent of clinical findings depends on the cause, severity and duration of hypothyroidism. An elevated TSH>20 microm Iu/L and a decreased concentration of T4 confirms the diagnosis of CH. Infants with permanant abnormalities of thyroid function mostly have a serum TSH concentration > 50 microm Iu/L. Ultrasonography, thyroid scintigraphy, bone x ray of the knee and serum thyroglobulin concentration are the other essentials after diagnosis to clarify the status of the thyroid and the severity of hypothyroidism. The higher doses of 10- 15 microm g/kg/day and the commencement of treatment before 2 weeks gave rise to better long term outcome of CH patients. In the follow up of the patients noncompliance is the most important problem and serum freeT4 or T4 and TSH should be obtained at each visit to adjust the doses of L-thyroxine. Still a small number of patients with severe hypothyroidism in utero or reflected by clinical signs and symptoms extremely low T4 levels and delayed bone age may have intellectual deficits despite normal intelligence.
 ...
PMID:Congenital hypothyroidism clinical aspects and late consequences. 1644 57

Congenital hypothyroidism (CH) occurs in approximately 1:2,000 to 1:4,000 newborns. The clinical manifestations are often subtle or not present at birth. This likely is due to trans-placental passage of some maternal thyroid hormone, while many infants have some thyroid production of their own. Common symptoms include decreased activity and increased sleep, feeding difficulty, constipation, and prolonged jaundice. On examination, common signs include myxedematous facies, large fontanels, macroglossia, a distended abdomen with umbilical hernia, and hypotonia. CH is classified into permanent and transient forms, which in turn can be divided into primary, secondary, or peripheral etiologies. Thyroid dysgenesis accounts for 85% of permanent, primary CH, while inborn errors of thyroid hormone biosynthesis (dyshormonogeneses) account for 10-15% of cases. Secondary or central CH may occur with isolated TSH deficiency, but more commonly it is associated with congenital hypopitiutarism. Transient CH most commonly occurs in preterm infants born in areas of endemic iodine deficiency. In countries with newborn screening programs in place, infants with CH are diagnosed after detection by screening tests. The diagnosis should be confirmed by finding an elevated serum TSH and low T4 or free T4 level. Other diagnostic tests, such as thyroid radionuclide uptake and scan, thyroid sonography, or serum thyroglobulin determination may help pinpoint the underlying etiology, although treatment may be started without these tests. Levothyroxine is the treatment of choice; the recommended starting dose is 10 to 15 mcg/kg/day. The immediate goals of treatment are to rapidly raise the serum T4 above 130 nmol/L (10 ug/dL) and normalize serum TSH levels. Frequent laboratory monitoring in infancy is essential to ensure optimal neurocognitive outcome. Serum TSH and free T4 should be measured every 1-2 months in the first 6 months of life and every 3-4 months thereafter. In general, the prognosis of infants detected by screening and started on treatment early is excellent, with IQs similar to sibling or classmate controls. Studies show that a lower neurocognitive outcome may occur in those infants started at a later age (> 30 days of age), on lower l-thyroxine doses than currently recommended, and in those infants with more severe hypothyroidism.
 ...
PMID:Congenital hypothyroidism. 2053 82