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)

A defect in the synthesis of dihydrobiopterin was detected in an Arab girl, ascertained through high blood phenylalanine level on neonatal screening. An oral loading test with tetrahydrobiopterin (BH4) caused a significant fall in her blood phenylalanine and a rise in tyrosine concentrations. Her blood biopterin levels were low. In urine and cerebrospinal fluid (CSF) very high neopterin and low biopterin levels were observed. A deficiency of metabolites of neurotransmitters, serotonin and dopamine, was observed in CSF and urine. The patient was given replacement therapy of BH4, 5-hydroxytryptophan, and L-dopa with carbidopa starting from the age of 16 to 18 weeks. On this treatment the blood phenylalanine levels dropped to the desired range, while in urine and CSF a satisfactory rise of neurotransmitter metabolites was observed. In spite of this biochemical control, the patient developed neurological symptoms with myoclonic jerks and changes in muscle tone and presented severe cerebral damage with mental retardation. She died suddenly at the age of 38 weeks.
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PMID:Malignant phenylketonuria due to defective synthesis of dihydrobiopterin. 387 52

We report our experience with the deficiency of 6-pyruvoyltetrahydropterin synthase, the most common form of tetrahydrobiopterin deficiency. We investigated 5200 patients suspected of having some inborn error of metabolism in a 10-year period, and detected 30 cases (from 28 sibships) of hyperphenylalaninaemias, HPA. From these, 4 sibships (5 patients) were affected by deficiency of 6-pyruvoyltetrahydropterin synthase. All of them were ethnically mixed, with some European ancestry detected in all. The age of diagnosis ranged from 2 to 9 years, and all were initially referred for investigation by having mental retardation and seizures. All of them showed low urinary biopterin levels and a marked elevation of neopterin. Although we detected only a few cases of HPA (30), 5 cases of 6-pyruvoyltetrahydropterin account for almost 20% of this total. The literature, however, reports a proportion of around 0.5%. As the frequency of classical phenylketonuria in our region is similar to that found in Caucasians (1/12,500), we believe that the frequency of this disease in South Brazil may be higher than expected (of the order of 1/400,000). We speculate that this finding could be related to a genetic drift (or founder effect).
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PMID:Possible high frequency of tetrahydrobiopterin deficiency in south Brazil. 796 77

In patients with neurodegenerative disorders, namely Alzheimer's disease and Huntington's disease, we compared serum concentrations of tryptophan, kynurenine and the kynurenine per tryptophan ratio with concentrations of soluble immune activation markers. Significantly lower tryptophan concentrations were observed in the patients, and lower tryptophan levels as well as higher kynurenine levels and higher kynurenine per tryptophan ratios correlated with higher concentrations of neopterin, and soluble receptors for TNF and interleukin-2. In both groups of patients tryptophan concentrations correlated inversely with the degree of mental retardation. No such association existed for the duration of the disease. The data show that systemic chronic immune activation in patients with Alzheimer's disease and Huntington's disease is associated with significant degradation of tryptophan, which is most likely due to activation of indoleamine (2,3)-dioxygenase by immunologic stimuli. Further studies will be necessary to investigate a potential role of tryptophan degradation in the pathogenesis of neurodegenerative disorders.
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PMID:Degradation of tryptophan in neurodegenerative disorders. 1072 Oct 50

Downs syndrome (DS) is the most frequent human chromosomal abnormality and is associated with mental retardation. Some evidence indicates that certain inflammatory molecules may be increased in DS. Proinflammatory and vasoactive molecules in the blood of non demented subjects with DS were measured in the present investigation. Plasma levels of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1) and C reactive protein (CRP) were measured in child (2-14 years), adult (20-50 yrs) and elderly (> 60 yrs) DS subjects. Increased plasma levels of IL-6 and MCP-1 were present in DS. Plasma levels of VEGF were increased only in DS adults. Positive linear correlation between IL-6 and MCP-1 levels was present. However, no subclinical inflammation was apparent in DS, since neopterin and CRP levels were within the normal range. An altered regulation of these molecules might interfere with some processes involved in cognitive performances of DS subjects.
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PMID:Altered vessel signalling molecules in subjects with Downs syndrome. 1656 56

6-Pyruvoyltetrahydropterin Synthase (PTPS) deficiency is the most common cause of hyperphenylalaninemia due to tetrahydrobiopterin deficiency. The presenting symptoms of PTPS deficiency are mental retardation, convulsions, disturbance of tone and posture, drowsiness, irritability, abnormal movements, hypersalivation, and swallowing difficulties(1-3). The authors reported the first two cases of PTPS deficiency in Thailand. Both cases were male infants who showed phenylalanine levels of 25.23 mg/dl and 23.4 mg/dl respectively. The urinary pterins analysis showed low biopterin and high neopterin. The percentage of urinary biopterin was also found to be very low. The mutation analysis of the first case revealed a point mutation of exon 4, a homozygous C to T transition at nucleotide 200 in codon 67 (T67M), and the second case showed a compound heterozygous of exon 4, C to A transition at nucleotide 200, and exon 5, C to T transition at nucleotide 259 of the PTS gene confirming that they had PTPS deficiency. Treatment was started with neurotransmitters and a low phenylalanine diet. Family carriers were detected by means of urinary pterins determination and mutation analysis.
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PMID:6-pyruvoyltetrahydropterin synthase deficiency two-case report. 1685 Jun 90