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)

Two cases of tyrosinaemia with eye and skin lesions typical of the Richner-Hanhart syndrome are described. The patients are a 29- and 26-year-old brother and sister. They do not show neurological abnormalities or mental retardation. Parents are not consanguineous and family history is negative for similar conditions. The diagnosis of type II tyrosinaemia was based upon an increase of blood tyrosine (14-16mg/100 ml), tyrosinuria and absence of liver and kidney abnormalities. The treatment with a low tyrosine phenylalanine diet has resulted in a disappearence of the ocular manifestations while the cutaneous lesions are much improved.
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PMID:Familial tyrosinaemia with eye and skin lesions. Presentation of two cases. 2 May 95

The hyperphenylalaninemias are caused by the defect of either phenylalanine hydroxylase (PAH) or tetrahydrobiopterin (BH4) cofactor. The former is diagnosed as phenylketonuria (PKU) or benign hyperphenylalaninemia, based on the serum phenylalanine values. The latter, so called malignant hyperphenylalaninemia, includes three enzyme defects, dihydropteridine reductase (DHPR), 6-pyruvoyl tetrahydropterin synthase (PT PS) and guanosine triphosphate cyclohydrolase (GTP-CH). Excess phenylalanine and its metabolites cause brain damage before 6 years of age. Deficiency of BH4 impairs two other hydroxylases (tyrosine and tryptophan), and severe neurological symptoms develop because of the lack of neurotransmitters. Tyrosinemia I, II, and III are different enzyme defects, fumarylacetoacetate hydrolyase (FAH), hepatic tyrosine aminotransferase (TAT), and 4-hydroxyphenylpyruvate acid oxidase, respectively. Tyrosinemia I is associated with severe involvement of the liver, kidney and central nervous system. Tyrosinemia II has mental retardation, palmar hyperkeratosis and corneal ulcers. Tyrosinemia III has mild mental retardation but no eye or skin manifestations.
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PMID:[The metabolic basis of the hyperphenylalaninemias and tyrosinemia]. 135 1

Tyrosinemia type II (Richner-Hanhart syndrome, RHS) is a disease of autosomal recessive inheritance characterized by keratitis, palmoplantar hyperkeratosis, mental retardation, and elevated blood tyrosine levels. The disease results from deficiency in hepatic tyrosine aminotransferase (TAT; L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5), a 454-amino acid protein encoded by a gene with 12 exons. To identify the causative mutations in five TAT alleles cloned from three RHS patients, chimeric genes constructed from normal and mutant TAT alleles were tested in directing TAT activity in a transient expression assay. DNA sequence analysis of the regions identified as nonfunctional revealed six different point mutations. Three RHS alleles have nonsense mutations at codons 57, 223, and 417, respectively. One "complex" RHS allele carries a GT----GG splice donor mutation in intron 8 together with a Gly----Val substitution at amino acid 362. A new splice acceptor site in intron 2 of the fifth RHS allele leads to a shift in reading frame.
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PMID:Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II. 135 62

Two sibs with palmo-plantar keratosis and dendritic corneal opacities, previously described as suffering from Richner-Hanhart syndrome by other authors, about 25 years ago, showed increased plasma and urine tyrosine levels. Their neurological and mental features were within normal limits. A comprehensive review of the literature showed a total of 47 cases of fully documented tyrosinemia type II; 8 more patients also had the clinical features of the disease, but aminoacidemia had never been observed. The importance of early diagnosis is stressed, since a low tyrosine-phenylalanine diet dramatically improves the symptoms and may prevent mental retardation.
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PMID:Tyrosinemia type II in two cases previously reported as Richner-Hanhart syndrome. 294 25

Type II tyrosinemia (Richner-Hanhart syndrome) is a familial aminoacid disorder, clinically characterized by ocular changes (keratitis), palmo-plantar hyperkeratosis, no constant mental changes with mental deterioration, abnormal urinary excretion and high serum tyrosine level in consequence of the absence of tyrosine-aminotransferase. Almost 20 families have been described in the literature of which 50% are of Italian origin, suggesting that this disorder is particularly frequent in our country. We report a family with 2 affected members with typical clinical and biochemical findings (keratitis, palmo-plantar hyperkeratosis, abnormal urinary and serum tyrosine concentrations), not suffering from mental retardation. Clinical symptoms completely disappeared after the decrease of urinary and serum tyrosine levels following a tyrosine- and phenylalanine-free diet. These cases are compared with those reported in literature, and the usefulness of diet for the improvement of clinical and metabolic symptoms is discussed.
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PMID:The effect of diet on the ophthalmological, clinical and biochemical aspects of Richner-Hanhart syndrome: a morphological ultrastructural study of the cornea and the conjunctiva. 365 59

The Richner-Hanhart syndrome corresponds to a tyrosine elevation in serum due to deficit in soluble tyrosine aminotransferase in liver cells. This new enzymopathy which is transmitted in an autosomal recessive mode is called oculocutaneous tyrosinosis. It is curable by a poor diet in tyrosine and its precursors. The diagnosis has been invoked in a 18 months old girl, on the association of punctuate palmar and plantar keratosis, dentritic ulcerated keratitis, and mental retardation. The diagnosis is confirmed by elevation of tyrosinemia to 52 mgs/100 mls associated with a high urinary elimination of tyrosine and plenylcetonic acid. Absences of anomaly in the metabolism of methionin and hepatorenal absence of disturbance of hepatorenal system is characteristic. The keratosis accompany orthokeratotic hyperkeratosis. The keratinocytes show 2 types of anomaly ranged in strates in the epiderm. Intracytoplasmic vacuoles which include or lead to pseudomyelinic formations extend progressively from the mitochondrial alterations in the epidemial basal layers. Bulky polyhedral electron dense particles are found in the cytoplasm of the superficial keratinocytes. Most of these aspects have been demonstrated anteriorly in the keratinocytes and the cornea; on the other hand, signs of mitochondrial sulferance had not been observed. The genesis of these cellular alterations based on the liberation of lysosomial enzymes by the action of crystals of tyrosine has been suggested by Goldsmith from experimental facts. However, it seems the mitochondrial defect occurs outside this mechanism.
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PMID:[Oculo-cutaneous tyrosinosis (Richner-Hanhart syndrome). Histo-pathological study of a case]. 611 39

Four cases of tyrosinaemia with cutaneous manifestations, but without ocular involvement, are reported in a family with consanguineous parents. The tyrosine levels in the serum and in the urine were normal in both parents, while in the offsprings the tyrosine levels were elevated 7 1/2-13 times in the serum and 3-13 times in the urine. Although the serum tyrosine levels in our cases were higher than most of the cases reported in the literature the eyes of all our patients were normal. The skin manifestations were very impressive, and varying degrees of mental retardation were present in all patients. The patients put on a low-protein diet improved considerably and have been kept symptom-free for 1 1/2 years. The possible implication of the discrepancy between the high serum levels and lack of ocular changes is discussed. Our results suggest that the Richner-Hanhart syndrome may include more than one distinct biochemical entity.
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PMID:Richner-Hanhart syndrome (tyrosinaemia-II) (report of four cases without ocular involvement). 645 6

Three children (6 eyes) with systemic tyrosinemia who presented with a diagnosis of herpes simplex keratitis are described. Two of the patients underwent extensive treatment for herpes simplex keratitis until their defects in tyrosine metabolism were discovered. All three children responded favorably to a low-tyrosine diet. These cases illustrate the typical corneal findings of the Richner-Hanhart syndrome (pseudodendritic keratitis, hyperkeratotic skin lesions of the palms and sole without mental retardation). The findings in these three patients were similar to those cases previously reported in the literature except none had mental retardation. The ophthalmologist confronted with a young child with bilateral dendritiform keratitis should request evaluation of the serum tyrosine levels.
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PMID:Pseudodendritic keratitis and systemic tyrosinemia. 645 71

Four cases of tyrosinaemia type II (Richner-Hanhart syndrome) are reported. This syndrome consists of corneal erosions, palmar and plantar hyperkeratoses, and sometimes mental retardation. Presentation with photophobia and dendritic corneal ulceration or circumscribed palmoplantar keratoderma should alert the physician to the possible diagnosis of tyrosinaemia II. Early diagnosis is important, as the clinical picture can be modified by dietary restriction.
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PMID:Tyrosinaemia II. 648 66

The Richner-Hanhart syndrome corresponds to a tyrosine elevation in serum due to a defect in soluble tyrosine amino-transferase in liver cells. This new enzymopathy which is transmitted in an autosomal recessive mode is called oculo-cutaneous tyrosinosis. It is curable by a low diet in tyrosine and its precursors. The diagnosis has been clinically suggested in an 18 months old girl, by the association of punctate palmar and plantar keratosis, dendritic ulcerated keratitis, and mental retardation. The diagnosis was established by elevation of tyrosinemia up to 52 mg/100 ml associated with a high urinary elimination of tyrosine and phenylcetonic acid. Absence of anomaly in the metabolism of methionin and hepatorenal lesion is characteristic. The diagnosis was confirmed by the absence of soluble tyrosine aminotransferase in liver cells and by the effectiveness of the diet. The clinical keratosis corresponds histologically to a orthokeratotic hyperkeratosis. The keratinocytes show 2 types of anomalies ranged in the epiderm. Intracytoplasmic vacuoles which include or lead to pseudomyelinic formations extend progressively from the mitochondrial alterations in the epidemial basal layers. Bulky polyhedral electron dense particles are found in the cytoplasm of the superficial keratinocytes. Most of these images have been demonstrates anteriorly in the keratinocytes ant the corned; on the other hand, signs of mitochondrial anomaly had not been observed. The genesis of these cellular alterations based on the liberation of lysosomial enzymes by the action of crystals of tyrosine has been suggested by Goldsmith from experimental facts. However, it seems that the mitochondrial defect occurs outside this mechanism.
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PMID:[Changes in the keratinocytes in oculo-cutaneous tyrosinosis: Richner-Hanhart syndrome (author's transl)]. 723 83


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