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 5 9/12-year-old Mexican female with argininemia presented at 4 years of age with severe growth retardation, microcephaly, mental retardation, loss of ability to walk, spasticity and epileptiform electroencephalogram. At follow-up, blood ammonia was elevated only twice out of 30 determinations. Blood arginine was 544 to 1,074 mumol/l (normal 61 to 173); cerebrospinal fluid arginine was 88 mumol/l (normal 6 to 29); and urinary arginine, citruline and argininosuccinic acid were consistently elevated. Arginase activities in tissues from the propositus were 0.01 mU/mg hemoglobin in erythrocytes (normal 29.8 to 96.1); 9 mU/mg protein in liver (normal 1,522 to 5,491); and 5 mU/mg protein in stratum corneum (normal 2,856 to 7,556). The demonstration of arginase deficiency in liver and stratum corneum suggests a generalized deficiency and helps to explain the elevation of blood arginine. Therapeutic trials of orally administered lysine to enhance dibasic amino acid competition and of enzyme replacement using erythrocyte transfusion did not result in significantly decreased blood arginine or clinical improvement.
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PMID:Arginase deficiency in multiple tissues in argininemia. 62 88

A 21-month-old girl with physical and mental retardation is described. She excreted an increased amount of lysine in urine but no excessive quantities of arginine, ornithine, or cystine. Serum level of lysine was found to be low but the levels of the other amino acids were within normal limits. The endogenous renal clearance rates of amino acids showed a marked high value of lysine and normal values of the other dibasic amino acids. Oral loading test of amino acids revealed an imparied absorption of lysine and normal absorption of arginine, ornithine, and cystine in the intestine. These results indicate a specific defect in transport of lysine in the intestine as well as in the renal tubule.
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PMID:Lysine malabsorption syndrome: a new type of transport defect. 124 85

Glutaric aciduria is a disorcer of lysine, tryptophan, and hydroxylysine metabolism characterized by intermittent metabolic acidemia, dystonia, athetosis and mental retardation. It is due to a recessively inherited deficiency of glutaryl-CoA dehydrogeanse, the enzyme(s) which catalyze the dehydrogenation of glutaryl-CoA to glutaconyl-CoA and decarboxylation of the latter to crotonyl-CoA. Abnormal quantities of glutaric, beta-hydroxyglutaric, and glutaconic acids are found in the urine of these patients. The nature of the movement disorder prompted study of the effects of the abnormally excreted metabolites on brain glutamate decarboxylase, an enzyme implicated in the pathogenesis of Huntington's chorea. Glutamate decarboxylase activity was examined in rat and rabbit brain acetone powders, stabilized with pyridoxal phosphate and glutathione. Glutarate, beta-hydroxyglutarate, and glutaconate were competitive inhibitors of this emzyme, Ki values being 1.3 X 10(-3) mol/l, 2.5 X 10(-4) mol/l, respectively. This inhibition may explain the neurological accompaniments of this syndrome.
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PMID:Inhibition of brain glutamate decarboxylase by glutarate, glutaconate, and beta-hydroxyglutarate: explanation of the symptoms in glutaric aciduria? 124 44

An unusual association of Bardet-Biedl syndrome with cystinuria was described in one patient. A 21-year-old male was admitted to hospital because of renal failure, severe deterioration of visual acuity, polydactyly, brachydactyly, and mental retardation. Laboratory investigations revealed a serum creatinine of 292 mumol/L (3.3 mg/dL) and a GFR of 25 mL/min per 1.73 m2. Quantitative ion exchange chromatography demonstrated an increased urinary excretion rate of cystine, lysine, arginine, and ornithine. The ophthalmologic examination showed a severe atypical retinal dystrophy. Visual acuity was severely deteriorated and the patient could only count the examining physician's fingers. The patient had been previously evaluated at the age of 7 years for polyuria, polydipsia, and growth failure. His workup at that time demonstrated nephrogenic diabetes insipidus, normal GFR, and a urinary amino acid pattern consistent with the cystinuric phenotype. There was mental retardation notwithstanding the normal ophthalmologic examination. Intravenous pyelography showed calyceal clubbing, calyceal cysts, and lobulated renal outlines of the fetal type. The patient was evaluated again at the age of 13 years for deterioration of visual acuity and the ophthalmologic examination showed an atypical retinal dystrophy, with sparse pigmentation, central and peripheral atrophy, attenuated vessels, and marked optic disk pallor. To our knowledge the association of Bardet-Biedl syndrome with cystinuria has never been reported. It is unlikely that cystinuria may have contributed to the kidney damage. The possibility that mental retardation has been induced or aggravated by cystinuria cannot be excluded.
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PMID:Bardet-Biedl syndrome and cystinuria. 146 12

We report cystinuria and symptoms of cerebellar atrophy in a 45-year-old man. His parents were first cousins, and many members of his family had stones of urinary tract or gait impairment. Neurological examination disclosed cerebellar signs resembling those of spinocerebellar degeneration. Urinalysis disclosed high cystine, lysine, ornitine and arginine output. Cystine was 1153.8 micro mol/day (normal range, 22-170); lysine, 3443.9 (normal range, 44-1000); ornitine, 283.8 (normal range, 7-40); and arginine, 154.0 (normal range, 9-50). Neurological complications reported to be associated with cystinuria include mental retardation, muscular dystrophy, hypotonia and dwarfism, mongolism, paroxysmal dyskinesia, myopathy, migraine, spastic paraplegia, multiple sclerosis, subacute combined degeneration and cranial polyneuropathy. Cerebellar signs have been reported in only two cases, and to our knowledge, this is the first case of cystinuria with cerebellar atrophy ever reported. Some common metabolic errors may have caused both disorders, although they also may have developed independently.
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PMID:[Cystinuria with symptoms of cerebellar atrophy--a case report]. 189 74

In a male infant with macrocephaly and dystonic cerebral palsy glutaric aciduria type I was detected by analysis of urine for organic acids. Glutaric aciduria type I is an inherited metabolic disorder of organic acids due to a defect of glutaryl-CoA-dehydrogenase in the intermediate metabolic step of lysine and tryptophan degradation. In the urine glutaric acid is usually accompanied by 3-hydroxy-glutaric acid in abnormal quantities. The enzyme defect in our patient was proved in cultured fibroblasts. In the cerebral computer tomography marked atrophy of bilateral frontotemporal regions could be demonstrated. The amount of urinary glutarat excretion decreased after protein but especially after lysine and tryptophan restriction in the diet. The administration of carnitine improved carnitine levels in blood and urine. Although the progression of neurological impairment could be stopped, dystonia and dyskinesis remained nearly unaltered. In spite of severe motor retardation, recognition and vocalisation were established. In the two year old patient mental retardation is relatively mild comparing with motor retardation. The administration of 100 or 200 mg Riboflavin/day was stopped, as it did not alter clinical symptoms or excretion of glutarat. Baclofen, an analogue of gamma-amino-butyric acid, was orally given (2 mg/kg/day) and improved dystonia, but did not influence organic aciduria. The neurological manifestations may be due in part to inhibition of neuronal glutamat decarboxylase by glutaric acid with decreased gamma-amino-butyric acid biosynthesis. The characteristic clinical symptoms with macrocephaly and dystonia and the very typical pattern of organic acids in urine are a challenge for rapid diagnosis and therapy.
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PMID:[Macrocephaly and dystonic cerebral palsy in a child with type I glutaric aciduria]. 194 71

We describe the molecular characterization of two mutations responsible for galactosemia, an inherited disorder of galatose metabolism that causes jaundice, cataracts, and mental retardation in humans. The coding region of galactose-1-phosphate uridylyltransferase (GALT; UDPglucose:alpha-D-galactose-1-phosphate uridylyltransferase, EC 2.7.7.12) was amplified by the polymerase chain reaction from total cDNA of a classic galactosemic individual and was characterized by direct sequencing of the products. Two missense mutations were identified: (i) replacement of valine-44 by methionine and (ii) replacement of methionine-142 by lysine. These mutations led to a drastic reduction in GALT activity when individual mutant cDNAs were overexpressed in a mammalian cell system, although full-length protein is synthesized in this assay. The two galactosemia mutations account for 3 of the 15 galactosemia alleles analyzed. These results suggest that galactosemia is caused by a variety of mutations, which might be responsible for the observed clinical heterogeneity of this disorder. We also present the molecular characterization of two GALT polymorphisms: (i) replacement of leucine-62 by methionine and (ii) replacement of asparagine-314 by aspartate. It appears that galactosemia mutations tend to occur in regions that are highly conserved throughout evolution while the polymorphisms change variable residues.
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PMID:Molecular basis of galactosemia: mutations and polymorphisms in the gene encoding human galactose-1-phosphate uridylyltransferase. 201 74

To clarify the effects of perinatal anoxia on the subsequent amino acid metabolism in the brain of children, free amino acid levels in the cerebrospinal fluid (CSF) were determined in 15 children diagnosed as having cerebral palsy and/or mental retardation with perinatal anoxia, and 58 control children without anoxia, aged from 4 days to 12 yrs. There was no significant difference in total amino acid levels between anoxic children and the controls. In the controls, the Gln level in CSF was high, Arg, Asp and Glu levels in CSF were almost the same during infancy and childhood, and the levels of Orn, Lys, His, Tau, Thr, Ser, Asn, Gly, Ala, Val, Met, Ile, Leu, Tyr and Phe in CSF decreased with age until pre-school age. In the newborns and infants among the anoxic children, the levels of most free amino acids in CSF were relatively high compared with those of the controls and, except Glu and Gln, decreased with age during infancy. The Orn, His, Gly, Tyr and Phe levels in CSF of anoxic children were lower than those of the controls in older infants. These results suggest that perinatal anoxia affected free amino acid patterns in CSF of newborns and infants and that the subsequent disturbance of amino acid metabolism in their brains remained after birth.
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PMID:The effect of perinatal anoxia on amino acid metabolism in the developing brain. Part II: The effect of perinatal anoxia on the free amino acid patterns in CSF of infants and children. 406 76

A large novel alpha-thalassemia-1 deletion which includes the zeta-, alpha 2-, alpha 1-, and theta 1-globin genes is described in a Black family living in Georgia and Florida. The deletion which was characterized by restriction enzyme analysis, extends 15 to 35 kb 5' and at least 35 kb 3' to the Cap site of the zeta-globin gene. Mental retardation was not observed. The deletion was present in a 35-year-old male with Hb H disease and his mother; the major hemoglobin type in the propositus was Hb G-Philadelphia or alpha (2)68(E12)Asn-->Lys beta 2 because his second chromosome carried the -alpha G(-3.7 kb) alpha-thalassemia-2 deletion.
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PMID:Black alpha-thalassemia-1: partial characterization of an approximately 80 kb deletion which includes the zeta- and alpha-globin genes. 790 Nov 83

We report myoclonic epilepsy with ragged-red fibers (MERRF) syndrome in a Chinese family with confirmed mitochondrial DNA point mutation. Six members of the family including the grandmother, two siblings, and three grandchildren were affected. Among them, action myoclonus was seen in five; short stature, muscle weakness, and mental retardation in four; lactic acidosis, hearing impairment, and ataxia in two; and seizures in one. Muscle biopsy from two affected siblings revealed ragged-red fibers and abundant subsarcolemmal mitochondria with paracrystalline inclusions. Pedigree analysis suggests a maternal transmission. Analysis of mitochondrial DNA showed a point mutation from A to G at the 8344th nucleotide position located in the tRNA(Lys) gene. To our knowledge, this is the first report of MERRF syndrome with such genetic defect from a Chinese family. The present and previous reports support the notion that mitochondrial DNA point mutation at the 8344th nucleotide position is the most common cause of MERRF syndrome.
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PMID:Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome: report of a Chinese family with mitochondrial DNA point mutation in tRNA(Lys) gene. 793 36


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