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)

Richner-Hanhart's syndrome (corneal dystrophies, palmoplantar keratoses, and mental retardation) is caused by high levels of L-tyrosine in the blood, probably due to a defect of soluble tyrosine aminotransferase. Biopsies of skin lesions of 3 cases revealed peculiar ultrastructural changes that were not found in controls and have not been recorded before. Thickening of the granular layer and increased synthesis of tonofibrils and keratohyalin occurred in all cases. In the ridged palmar or plantar skin large numbers of microtubules and unusually tight packing of tonofibrillar masses were regularly demonstrable, the latter containing tubular channels or inclusions of microtubules. It is assumed that increased cohesion and tight packing of tonofilaments could prevent normal spreading of keratohyalin and result in its globular appearance. No crystal formation was observed in epidermal keratinocytes nor was there lysosomal damage. A biochemical model to correlate these ultrastructural findings to known biochemical and clinical features is proposed. It is suggested that excessive amounts of intracellular tyrosine enhance cross-links between aggregated tonofilaments and modulate the number and stability of microtubules.
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PMID:Richner-Hanhart's syndrome: ultrastructural abnormalities of epidermal keratinization indicating a causal relationship to high intracellular tyrosine levels. 612 75

New ultrastructural observations are described in skin lesions of two brothers with Richner-Hanhart's syndrome (RHS). Physical examination of the two patients showed painful skin lesions of palms and soles combined with denderitic corneal ulceration and mental retardation. The diagnosis of RHS was confirmed biochemically with high tyrosine levels in both blood and urine. Examination by transmission electron microscopy revealed several abnormal ultrastructural changes in the epidermal cells. The horny cells contained heterogeneously, electron-dense cytoplasm with many lipid droplets. The granular cell cytoplasm contained abundant tonofibrils and keratohyaline granules. The spinous cell cytoplasm was vacuolated due to the presence of minute tyrosine crystals, which are known to have a lytic effect. The surrounding keratinocytes contained multilobed nuclei. The basal epidermal cells appeared normal except for Merkel cells, which were severely damaged by vacuolatio, also due to the presence of tyrosine crystals. This study showed that high tyrosine levels can induce several ultrastructural pathological changes in the epidermal cells, including the skin chemoreceptor Merkel cells.
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PMID:Richner-Hanhart's syndrome: new ultrastructural observations on skin lesions of two cases. 902 66

Tyrosinemia type II or Richner-Hanhart Syndrome (RHS) is an autosomal recessive disorder characterized by keratitis, palmoplantar keratosis, mental retardation, and elevated blood tyrosine levels. The disease is due to a deficiency of hepatic cytosolic tyrosine aminotransferase (TATc), an enzyme involved in the tyrosine catabolic pathway. Because of the high rate of consanguinity this disorder seems to be relatively common among the Arab and Mediterranean populations. RHS is characterized by inter and intrafamilial phenotypic variability. A large spectrum of mutations within TATc gene has been shown to be responsible for RHS. In the present study, we report the clinical features and the molecular investigation of RHS in three unrelated consanguineous Tunisian families including 7 patients with confirmed biochemical diagnosis of tyrosinemia type II. Mutation analyses were performed and two novel missense mutations were identified (C151Y) and (L273P) within exon 5 and exon 8, respectively. The 3D-structural characterization of these mutations provides evidence of defective folding of the mutant proteins, and likely alteration of the enzymatic activity. Phenotype variability was observed even among individuals sharing the same pathogenic mutation.
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PMID:Clinical and mutational investigations of tyrosinemia type II in Northern Tunisia: identification and structural characterization of two novel TAT mutations. 1657 53