Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histidinemia was found in 3 of 4 siblings in one family, while a fatal encephalopathy with mental retardation was present in two of them and in the fourth child who did not have histidinemia. Biochemical studies of the histidinemic subjects showed elevated histidine levels in urine, CSF, and brain, while in a few urine samples histidine related imidazole compounds were found. Plasma levels of other amino acids were positively correlated with plasma histidine levels. Obesity and heart abnormalities appeared to be associated with the encephalopathy, which is probably of a new type. The histidinemia appears to be unrelated to the mental retardation or the encephalopathy in this family.
 ...
PMID:Sibship with histidinemia and an unrelated encephalopathy. Clinical and biochemical studies. 61 85

This study was performed to investigate 1) technical modification of Guthrie method for mass screening to detect histidinemia, 2) patients with histidinemia in view of genetic and biochemical aspects, and 3) therapy of histidinemia in newborn infants. Guthrie method was the useful method for mass screening of histidinemia in newborn infants. It is possible to measure blood level of histidine using by Subutilis spore ATTCC 6633 instead of ATCC 6051. Mass screening of histidinemia was done in about 20,000 newborn infants in Hokkaido, and one case of histidinemia, which was first case in Japan found by this method, was observed. In a case of 5 year-old boy with clinical histidinemia, in whom serum histidine level was 12.1 mg/kl, histidase activity of stratum corneum was not detectable, FIGLU and urocanic acid in urine and urocanic acid in sweat were not detected, the half life of histidine at intravenous histidine loading test was too long to measure. But in other case of 13 year-old boy without clinical signs of histidinemia, elder brother of former case, serum histidine level was 4.7 mg/dl, histidase activity was 11% of normal control, excretion of FIGLU and urocanic acid in urine, and urocanic acid in sweat were observed, and the half life of histidine was 5 hours and 50 minutes (normal: 2 hours and 20 minutes). In both cases, Tryptophan absorption and metabolism were not influenced by high level of blood histidine. Therapy with low histidine milk was made in 3 cases of affected infants. When histidine was given orally in dose of 30-35 mg/kg/day, serum histidine level was down to 3-5 mg/dl in a week in all cases, but in one case low proteinemia an anemia were observed. When histidine was orally given in a dose of 40-50 mg/kg/day, serum histidine level was well controlled. In all cases with histidine limited diets, mental retardation and growth retardation were not found.
 ...
PMID:[Clinical studies of histidinemia (author's transl)]. 679 Mar 99

Histidinemia is an inherited metabolic disorder caused by deficiency of histidase activity, which leads to tissue accumulation of histidine and its derivatives. Affected patients usually present with speech delay and mental retardation, although asymptomatic patients have been reported. Considering that the pathophysiology of the neurological dysfunction of histidinemia is not yet understood and since histidine has been considered a pro-oxidant agent, in the present study we investigated the effect of histidine and one of its derivatives, l-beta-imidazolelactic acid, at concentrations ranging from 0.1 to 10 mM, on various parameters of oxidative stress in cerebral cortex of 30-day-old Wistar rats. Chemiluminescence, total radical-trapping antioxidant potential (TRAP), thiobarbituric acid reactive substances (TBA-RS), and the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were measured in tissue homogenates in the presence of l-histidine or l-beta-imidazolelactic acid. We observed that l-histidine provoked an increase of chemiluminescence and a reduction of TRAP at concentrations of 2.5 mM and higher, while TBA-RS measurement, GSH-Px, CAT and SOD activities were not affected. Furthermore, l-beta-imidazolelactic acid provoked antioxidant effects at high concentrations (5-10 mM) as observed by the reduction of chemiluminescence, although this compound enhanced chemiluminescence at low concentrations (0.5-1 mM). These results suggest that in vitro oxidative stress is elicited by histidine but only at supraphysiological concentrations.
 ...
PMID:Effects of histidine and imidazolelactic acid on various parameters of the oxidative stress in cerebral cortex of young rats. 1503 81

Histidinemia (MIM235800) is characterized by elevated histidine in body fluids and decreased urocanic acid in blood and skin and results from histidase (histidine ammonia lyase, EC 4.3.1.3) deficiency. It is the most frequent inborn metabolic error in Japan. Although the original description included mental retardation and speech impairment, neonatal screening programs have identified the majority of histidinemic patients with normal intelligence. Molecular characteristics of histidase in histidinemia have not been determined, and cytogenetically visible deletions of 12q22-24.1 in which histidase gene resides have not been identified in histidinemic patients. In order to investigate whether individuals with this disorder have small deletions, additions, or point mutations in the histidase gene, we screened genomic DNA isolated from 50 histidinemic individuals who were discovered by the neonatal screening program. The methods employed included polymerase chain reaction (PCR) amplification of exons 1-21 of the histidase gene, followed by mutation detection enhancement gel electrophoresis and sequencing of the PCR products displaying heteroduplex bands. Four missense mutations (R322P, P259L, R206T, and R208L), two exonic polymorphisms (T141T c.423A-->T and P259P c.777A-->G), and two intronic polymorphisms (IVS6-5T-->C and IVS9+25A-->G) were identified. The frequencies of each polymorphism estimated either by dot blot allele-specific oligonucleotide hybridization, restriction enzyme digestion, or direct sequencing of the PCR products amplified from 50 unrelated normal individuals were 0.28, 0.30, 0.40, and less than 0.01, respectively. Mutation analysis of one family demonstrated that the patient inherited R322P from the mother and P259L from the father. This report describes the first mutations occurring in the coding region of the histidase structural gene in patients with histidinemia.
 ...
PMID:Molecular characterization of histidinemia: identification of four missense mutations in the histidase gene. 1580 99

Histidinemia is an inherited metabolic disorder biochemically characterized by high concentrations of histidine in biological fluids. Usually affected patients are asymptomatic although some individuals have mental retardation and speech disorders. Considering the high prevalence of histidinemia and the scarce information on the effects of maternal histidinemia on their progeny, we investigated various parameters of oxidative stress in brain cortex and hippocampus of the offspring from female rats that received histidine (0.5 mg/g of body weight) in the course of pregnancy and lactation. At 21 days of age we found a significant increase of thiobarbituric acid reactive substances (TBARS), 2',7'-dihydrodichlorofluorescein oxidation, superoxide dismutase (SOD) activity, catalase (CAT) activity, total sulfhydryls and glutathione (GSH) content in cerebral cortex and hippocampus. We also verified that at 60 days of age, GSH, SOD and total sulfhydryls returned to normal levels in brain cortex, while the other parameters decreased in the same structure. In the hippocampus, at 60 days of age GSH returned to normal levels, CAT persisted elevated and the other parameters decreased. These results indicate that histidine administration to female rats can induce oxidative stress in the brain from the offspring, which partially recovers 40 days after breastfeeding stopped.
 ...
PMID:Administration of histidine to female rats induces changes in oxidative status in cortex and hippocampus of the offspring. 2223 70