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 citrullinemia were reported. Case 1 was an one month old female. Her clinical course and findings were different from the fulminant type of neonatal citrullinemia reported in predominantly Caucasian countries. Our patient was well controlled under a low protein diet and essential amino acids till 9 months of age, but unfortunately she died of Reye's like syndrome. Case 2 was 31 year old male (at the time of death). He was admitted to our hospital because of hyperammonemia and mental retardation. By subsequent laboratory investigations he was diagnosed as having adult type of citrullinemia and died of hepatoma. Enzymological analysis revealed that argininosuccinate synthetase (ASS) activities in the liver tissues of the patients decreased to 40% (Case 1), 20% (Case 2) compared with those in control liver tissues. The other urea cycle enzyme activities were all within normal range. ASS activities in the kidney and brains of the two cases were within normal range. The kinetic constant values of ASS for three substrates in the tissues of liver and kidney were all normal. Results of immunochemical analyses indicated that citrullinemia in our patients was caused by a quantitative deficiency of ASS associated proteins of the liver and kidney tissues as to the molecular weight.
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PMID:Citrullinemia: quantitative deficiency of argininosuccinate synthetase in the liver. 373 4

Three female infants with citrullinemia were followed clinically, biochemically and by electroencephalography. All three had episodes of vomiting, lethargy and hyperammonemia shortly after birth. The two more severe cases developed convulsions. They were saved by peritoneal dialysis, or repeated exchange transfusions followed by dietary adjustment. Multifocal spikes or repetitive paroxysmal activity of various kinds were seen in the EEGs at times of crisis. There was a lag in the EEG returning to normal after ammonia levels had returned to normal. Citrulline remained elevated in all cases. Follow-up over years revealed mild spasticity, mental retardation and, in one case, cortical atrophy.
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PMID:The EEGs of infants with citrullinemia. 399 77

A simple enzyme-multiple auxotroph assay has been developed for the identification of newborn infants with several of the inherited metabolic defects in the Krebs cycle for the detoxification of ammonia and in the ornithine metabolic pathway. This mass screening test is used with dried filter paper blood specimens and can easily be added to existing multiple testing programs presently used in screening for phenylketonuria or congenital hypothyroidism. This assay can be used to detect patients with citrullinemia, argininosuccinic acid lyase deficiency, and argininemia. In addition to these urea cycle disorders, the several types of ornithinemia, which can result in gyrate atrophy of the retina or mental retardation, should be detectable with this assay. The strengths and weaknesses of this assay are discussed and a large-scale pilot screening trial is proposed.
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PMID:A neonatal screening test for argininosuccinic acid lyase deficiency and other urea cycle disorders. 712 51

In 471 adult mentally retarded adult patients (mean age 46 years; 92.6% males) living in an institution for the mentally retarded, a clinical examination, cytogenetic and molecular studies were done. 306 patients were screened for metabolic disorders. In 7 additional patients a metabolic disorder (phenylketonuria (n = 5), mucopolysaccharidosis type III (Sanfilippo syndrome, type A) (n = 1) and mucopolysaccharidosis type VII (Sly syndrome) (n = 1)) was diagnosed in the past. The abnormal metabolic findings in this group of 313 patients were classified in three categories and the clinical findings are reported: 1. metabolic disorders as the cause of mental retardation (MR), 2. metabolic disorders not explaining the MR, and 3. metabolic abnormalities of unknown significance. The first two groups included 16 patients, i.e. 26.2% of the group of monogenic disorders and 3.4% of the total population: phenylketonuria (PKU) (n = 5), S-sulfocysteinuria (n = 3), mucopolysaccharidosis type III (Sanfilippo syndrome, type A) (n = 1) and Gm1-gangliosidosis type 3 (n = 1) (first group), and mucopolysaccharidosis type VII (Sly syndrome) (n = 1), Niemann-Pick syndrome, type B (n = 1), cystinuria (n = 1) and hyperprolinemia type 1 (n = 3) (second group). The third group included patients with citrullinemia (n = 2), methionine sulphoxide reductase deficiency (n = 1), ornithinemia (n = 1), glycinuria (n = 20), neuraminaciduria (n = 8), uraciluria (n = 6) and diabetes mellitus (n = 2). Screening for Congenital Disorders of Glycosylation (CDG) in 144 patients and for Smith-Lemli-Opitz syndrome (SLO) in a selected group of 6 patients was normal. Of the total group of 306 patients screened for inborn errors of metabolism, only 5 (1.6%) were found with a true metabolic disorder. These 5 patients presented clinical symptoms, neurodegenerative or behavioural problems, indicating further metabolic screening. The present study illustrates that a selected group of patients with mental retardation of unknown origin are candidates for metabolic screening, especially if aberrant behaviour, neurodegenerative problems or dysmorphic features are present.
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PMID:Metabolic studies in older mentally retarded patients: significance of metabolic testing and correlation with the clinical phenotype. 1133 72

Type II citrullinemia (CTLN2) is characterized by a deficiency of argininosuccinate synthetase (ASS) in the liver. Mutation analysis of the SLC25A13 gene, which is responsible for CTLN2, provides a rapid and accurate diagnosis. We describe clinical, biochemical and histologic features of two patients, whose diagnosis was finally made by mutation analysis. They initially presented with symptoms related to hyperammonemia at 16 to 22 years of age. A patient had shown mental retardation and growth failure from early childhood. Laboratory findings including amino acids, were characteristic, such as elevated citrulline, arginine, and lysine concentrations, but definitive diagnosis had not been made. The patients died of liver cirrhosis and hepatoma at 31 and 34 years old, respectively. Fatty change in the hepatocytes was commonly observed in the autopsied specimens. ASS activity was decreased in the liver of both patients, and a concomitant decrease of arginase activity was found in one case. Investigation for the SLC25A13 mutation revealed that one patient was homozygous for IVS11 + 1G>A, and the other was compound heterozygote (851del4/S225X). Comparison of genetic, enzymatic and biochemical data among various cases of CTLN2 will be essential to understand the real nature of the disease.
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PMID:Application of mutation analysis for the previously uncertain cases of adult-onset type II citrullinemia (CTLN2) and their clinical profiles. 1251 93

The known cases of mental retardation which exhibit a genetically determined biochemical lesion were reviewed. Twenty-two inborn errors of metabolism with associated mental defect have been described to date, 12 of these within the past decade. Improved procedures for diagnosis and therapy make this area of investigation a promising one for clinicians, biochemists and geneticists. During a screening program for amino aciduria, a "new" metabolic defect, citrullinuria, was detected in a mentally retarded child. This condition is characterized by the presence of citrulline in the urine, blood and cerebrospinal fluid in concentrations 50- to 100-fold greater than normal. Although the amounts of citrulline excreted appear to be related to the protein intake, it was not possible to reduce the high citrulline concentration in the blood by dietary restrictions.
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PMID:Biochemical Genetics and Mental Retardation. 2032 25