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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

A deficiency of hepatic tyrosine aminotransferase in humans is responsible for a syndrome of keratitis, palmar and plantar erosions and hyperkeratosis and mental retardation. Serum tyrosine increases due to the enzymatic deficiency leads to the deposition of tyrosine crystals in the eye and cornea. This deposition and possible lysosomal activation leads to inflammation in the cornea and the skin. The syndrome can be reproduced in animals who are fed a high tyrosine diet. The interaction of tyrosine crystals with membrane-bound particles can be studied in vitro with lysosomes and erythrocytes.
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PMID:Molecular biology and molecular pathology of a newly described molecular disease--tyrosinemia II (the Richner-Hanhart syndrome). 2 31

Tyrosine-induced eye and skin lesions in man are an autosomal, recessive, inherited syndrome associated with tyrosinemia, tyrosinuria, and increased urinary excretion of tyrosine metabolites. Patients have mild to severe keratitis and erosive and hyperkeratotic lesions on the palms and soles. The degree of involvement was variable in the small number of patients studied. Mental retardation is frequently a part of the syndrome. A low-tyrosine low-phenylalanine diet lowers blood tyrosine level and leads to healing of the skin and eye lesions. Early dietary treatment may prevent mental retardation.
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PMID:Tyrosine-induced eye and skin lesions. A treatable genetic disease. 13 41

Content of phenylalanine and tyrosine was increased in blood serum in mongolism. When 4 patients with mongolism and 10 healthy persons were loaded with 1-phenylalanine, content of the amino acid in blood serum of patients exceeded 1.5--2-fold that found in healthy persons within 4 and 6 hrs after the treatment. The hydroxylation rate of phenylalanine was lower in mongolism as compared to normal state; it corresponded to the rate of phenylalanine hydroxylation in atypical homo- and heterozygote patients bearing "phenylketonuria" gene and in patients with viral hepatitis. Concentration of tyrosine was distinctly higher in the impaired patients within 2--6 hrs after the loading as compared with the healthy persons. But content of tyrosine was increased only slightly in patients with mongolism during the loading and excretion of homogentisinic acid with urine was decreased. These data suggest that activity of phenylalanine hydroxylase system is impaired in liver tissue in mongolism. Excretion of phenylpyruvic acid with urine was not observed in the patients and healthy persons both before and during the amino acid loading. The data obtained suggest that impairment of phenylalanine and tyrosine turnover in mongolism appears to be one of the factors responsible for disturbance of neurotransmitter synthesis and to be related to development of mental retardation.
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PMID:[Disorders of phenylalanine and tyrosine metabolism in Down's syndrome]. 15 71

The justification hypothesis postulates that an individual genetically deficient in the synthesis of any of the 12 nonessential amino acids requires that amino acid in the diet just as a normal individual requires any essential amino acid. The deficiency of that single amino acid causes diminished protein synthesis. The hypothesis proposes that mental retardation develops during the late stage of fetal development, when the brain is growing most rapidly, as a result of the inability of the mother to deliver an appropriate amount of that nonessential amino acid to her fetus who, in turn, is unable to correct for this deficiency due to his genetic constitution. A paradigm is provided by the disease phenylketonuria in which the homozygote lacks the enzyme for synthesis of the nonessential amino acid tyrosine. By measuring the appearance of tyrosine in the plasma after an oral dose of phenylalanine, it is possible to show differential capability among siblings of known phenylketonuric children, in the expected Mendelian ratio. The mean IQ of the two-thirds of the siblings who were least able to convert phenylalanine to tyrosine (presumably heterozygotes) was 10 points lower than the mean IQ of the "normals," who were most able to synthesize tyrosine. The difference is statistically significant (P <0.01). The mean maternal IQ was halfway between that of the heterozygote group and that of the normal group, confirming the prediction of maternal-fetal interaction.
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PMID:Diet, genetics, and mental retardation interaction between phenylketonuric heterozygous mother and fetus to produce nonspecific diminution of IQ: evidence in support of the justification hypothesis. 27 41

Clinical manifestations in patients with carbonic anhydrase (CA) II deficiency include osteopetrosis, renal tubular acidosis, and cerebral calcification. Of the 39 reported cases of the carbonic anhydrase II deficiency syndrome, 72% were patients from North African and Middle Eastern countries, most, if not all, of whom were of Arabic descent. We have analyzed DNAs from members of six unrelated Arabic kindreds and found five to be homozygous and one heterozygous for a novel splice junction (donor site) mutation at the 5' end of intron 2. These findings suggest that a common "Arabic" mutation may be the predominant cause of CA II deficiency in this region. The mutation introduces a new Sau3A1 restriction site which allows polymerase chain reaction (PCR)-based diagnosis of this mutation that should be useful in diagnosis, carrier detection, and prenatal diagnosis. The presence of mental retardation and relative infrequency of skeletal fractures distinguish the clinical course of the patients with the Arabic mutation from those of the American and Belgian patients with the His 107-->Tyr mutation.
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PMID:A splice junction mutation in intron 2 of the carbonic anhydrase II gene of osteopetrosis patients from Arabic countries. 130 35

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

Deficiency of carbonic anhydrase II (carbonate hydro-lyase, EC 4.2.1.1) is the primary defect in the syndrome of osteopetrosis, renal tubular acidosis, and cerebral calcification. In this report we describe the molecular basis for carbonic anhydrase II deficiency in the American family in which the association of carbonic anhydrase II deficiency with this syndrome was first recognized. The three affected siblings from this family are compound heterozygotes, each having inherited two different mutations in the structural gene for carbonic anhydrase II. The paternal mutation is a splice acceptor site mutation at the 3' end of intron 5. The maternal mutation is a missense mutation in exon 3 that substitutes a tyrosine for histidine-107. We show that the mutant enzyme expressed in bacteria from the cDNA containing the His-107----Tyr mutation has detectable, though greatly reduced, activity. We suggest that residual activity of the His-107----Tyr mutant enzyme may explain the absence of mental retardation and the relatively mild phenotype of carbonic anhydrase II deficiency in affected members of this family.
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PMID:Molecular basis of human carbonic anhydrase II deficiency. 154 74

Phenylketonuria (PKU) has become a paradigm of a disease that can be identified by screening in the newborn period and treated to prevent serious complications. After many years of experience treating PKU, new challenges have emerged. It has become apparent that defective activity of phenylalanine hydroxylase leads to a spectrum of clinical presentations that has led to subclassifications of PKU. Blood phenylalanine greater than 1200 mumol/L usually indicates severe deficiency of phenylalanine hydroxylase and is often called "classical PKU." Blood phenylalanine levels between 600 and 1200 mumol/L lead to "atypical PKU." Cases where blood phenylalanine remains between 120 and 480 mumol/L on a normal diet are termed "benign hyperphenylalaninemia." A deficiency of the cofactor tetrahydrobiopterin (BH4), which is required for phenylalanine hydroxylase activity, leads to hyperphenylalaninemia. This cofactor is also required for the enzymatic hydroxylation of tyrosine and tryptophan. Cofactor defects account for only 1-3% of hyperphenylalaninemia, which has been termed "malignant PKU", but they must be identified so that appropriate treatment can be established. Long-term treatment of PKU is currently advised because loss of IQ, poor school performance, and behavior problems occur when blood phenylalanine levels increase. Therefore, there is reason to continue the diet as patients become older. When blood phenylalanine levels are elevated during pregnancy a "maternal PKU syndrome" may result. Babies born to untreated mothers with PKU are at risk for being small for gestational age with microcephaly, mental retardation and congenital heart defects. A national collaborative study for the treatment of maternal PKU is underway. The characterization of the gene for phenylalanine hydroxylase has added a new exciting chapter to the study of PKU.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phenylketonuria: screening, treatment and maternal PKU. 195 25


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