Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital hypothyroidism is the most prevalent endocrine disorder in the newborn and affects 1 in 3000-4000 newborns. Screening for congenital hypothyroidism is a major achievement of paediatrics because early diagnosis and treatment have resulted in normal development in nearly all cases. The cause of congenital hypothyroidism in the majority of newborns is unknown. However, in some patients the molecular basis of their congenital hypothyroidism has recently been clarified. In patients with congenital hypothyroidism and a normally developed thyroid gland, the autosomal recessive inheritance of loss-of-function mutations of genes encoding for the thyroid peroxidase gene, the sodium-iodide symporter gene and the pendrin gene have been identified. The autosomal recessive inheritance of loss-of-function mutations of the thyroid stimulating hormone (TSH) receptor as well as the dominant inheritance of mutations encoding for transcription factors have been identified in patients with defective thyroid development. Furthermore, it has become evident that in some patients with persistent mental retardation and neurological symptoms, defects of the transcription factor NKX2.1, which is expressed in the thyroid gland as well as in the CNS during embryonic development, cause both defective thyroid and CNS development resulting in persistent neurological and mental defects despite early diagnosis and treatment. Central hypothyroidism is a rare disease with an estimated frequency of not more than 1 in 50000 newborns. Central hypothyroidism can be due to recessive inheritance of loss-of-function mutations of the TSH-beta gene and to developmental defects of the hypothalamus or pituitary. In contrast to the previous assumption that isolated TSH deficiency will not lead to impaired mental development, identification of the molecular defects in central hypothyroidism has clearly demonstrated that some of these patients will have impaired mental development. Clarification of the molecular defects of thyroid development will help to explain the differences in outcome in patients with congenital hypothyroidism and to develop new diagnostic and therapeutic strategies to ensure adequate counselling and care for these patients.
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PMID:Neonatal thyroid disorders. 1256 17

Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by an early-infancy-onset diabetes mellitus associated with a variety of multisystemic clinical manifestations. Here, we present six patients with WRS, carrying the same homozygous mutation (EIF2AK3-W522X), from two unrelated Turkish families. This is the largest series of patients with the same mutation for this rare syndrome. In this communication we compare clinical features of these six patients with the other 34 patients who have been reported to date, and review the clinical features of WRS. All WRS patients presented first with symptoms of insulin dependent diabetes mellitus, with a mean age at onset of 2 months. All patients had skeletal dysplasia or early signs of it, and growth retardation. Many of the patients with WRS have been reported to have developmental delay, mental retardation, and learning difficulties; in contrast, none of our patients showed abnormal development at age up to 30 months. Acute attacks of hepatic failure were reported in 23 cases out of 37 patients; in 15 of those 23 cases an acute attack of renal failure accompanied the liver failure. Exocrine pancreatic deficiency has been reported in only four cases other than our four patients. Central hypothyroidism was observed in six of 28 cases. We propose that central hypothyroidism is not a component of WRS, but rather a reflection of euthyroid sick syndrome. Four of our patients experienced severe neutropenia, compared to only five of the 27 other cases, suggesting that the W522X mutation may be specifically associated with neutropenia. Other than the consistent features of diabetes mellitus and epiphyseal dysplasia, WRS patients are otherwise characterized by extensive phenotypic variability that correlates poorly to genotype.
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PMID:Wolcott-Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature. 2020 48