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)

There are many causes of lens dislocation in man. Amongst these are two inborn errors of sulfur amino acid metabolism, viz., homocystinuria and sulfite oxidase deficiency. To date nine patients have been found in whom a combined deficiency of sulfite oxidase and xanthine dehydrogenase was observed. This inherited disease is due to a defective synthesis of molybdenum cofactor, an essential component for the assembly of both enzymes. The main clinical symptoms of these patients were: facial dysmorphic features, severe feeding difficulties, mental retardation, abnormal muscle tone, severe seizures and myoclonia. Four out of nine patients had dislocated eye lenses. The main biochemical findings included hypouricemia, xanthinuria, an increased excretion of sulfite, thiosulfate, S-sulfocysteine, taurine and a decreased excretion of inorganic sulfate. The prognosis of the disease is poor; various attempts at treatment were not successful so far. Prenatal diagnosis by assay of sulfite oxidase in cultured amniotic fluid cells and by direct measurement of amniotic fluid S-sulfocysteine is possible.
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PMID:Absence of hepatic molybdenum cofactor. An inborn error of metabolism associated with lens dislocation. 387 98

Five patients with a combined deficiency of xanthine dehydrogenase, sulphite oxidase and, possibly, also of aldehyde oxidase are described. This remarkable coincidence of three inborn errors of metabolism in a single individual was demonstrated to result from a deficiency of the 'molybdenum cofactor', an essential constituent of all three enzymes. The main biochemical findings in these patients included: hypouricaemia, xanthinuria, an increased excretion of sulphite, thiosulphate and S-SUL-sulphocysteine and a decreased excretion of inorganic sulphate. Plasma molybdenum was normal. The ultimate diagnosis was made by the measurement of 'molybdenum cofactor' in a liver biopsy specimen in three out of five patients. The clinical hallmarks in these patients were: feeding difficulties, mental retardation, neurological symptoms, lens dislocation, an abnormal muscle tone, myoclonia and an abnormal physiognomy. The majority of these were already present in the neonatal period. So far, attempts at treatment have been unsuccessful.
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PMID:Absence of hepatic molybdenum cofactor: an inborn error of metabolism leading to a combined deficiency of sulphite oxidase and xanthine dehydrogenase. 641 78

A patient suffering from a combined deficiency of sulfite oxidase (sulfite dehydrogenase; sulfite:ferricytochrome c oxidoreductase, EC 1.8.2.1) and xanthine dehydrogenase (xanthine:NAD+ oxidoreductase, EC 1.2.1.37) is described. The patient displays severe neurological abnormalities, dislocated ocular lenses, and mental retardation. Urinary excretion of sulfite, thiosulfate, S-sulfocysteine, taurine, hypoxanthine, and xanthine is increased in this individual, while sulfate and urate levels are drastically reduced. The metabolic defect responsible for loss of both enzyme activities appears to be at the level of the molybdenum cofactor common to the two enzymes. Immunological examination of a biopsy sample of liver tissue revealed the presence of the xanthine dehydrogenase protein in near normal amounts. Sulfite oxidase apoprotein was not detected by a variety of immunological techniques. The plasma molybdenum concentration was normal; however, hepatic content of molybdenum and the storage pool of active molybdenum cofactor present in normal livers were below the limits of detection. Fibroblasts cultured from this patient failed to express sulfite oxidase protein or activity, whereas those from the parents and healthy brother of the patient expressed normal levels of this enzyme.
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PMID:Inborn errors of molybdenum metabolism: combined deficiencies of sulfite oxidase and xanthine dehydrogenase in a patient lacking the molybdenum cofactor. 699 82

Molybdenum cofactor deficiency (MoCoD) is a fatal disorder manifesting, shortly after birth, with profound neurological abnormalities, mental retardation, and severe seizures unresponsive to any therapy. The disease is a monogenic, autosomal recessive disorder, and the existence of at least two complementation groups suggests genetic heterogeneity. In humans, MoCoD leads to the combined deficient activities of sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase. By using homozygosity mapping and two consanguineous affected kindreds of Israeli-Arab origin, including five patients, we demonstrated linkage of a MoCoD gene to an 8-cM region on chromosome 6p21.3, between markers D6S1641 and D6S1672. Linkage analysis generated the highest combined LOD-score value, 3.6, at a recombination fraction of 0, with marker D6S1575. These results now can be used to perform prenatal diagnosis with microsatellite markers. They also provide the only tool for carrier detection of this fatal disorder.
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PMID:Localization of a gene for molybdenum cofactor deficiency, on the short arm of chromosome 6, by homozygosity mapping. 963 14

Cerebral hypoxia in the fetus and newborn results in neonatal morbidity and mortality as well as long-term sequelae such as mental retardation, seizure disorders, and cerebral palsy. In the developing brain, determinants of susceptibility to hypoxia should include the lipid composition of the brain cell membrane, the rate of lipid peroxidation, the presence of antioxidant defenses, and the development and modulation of excitatory amino acid neurotransmitter receptors such as the N-methyl-D-aspartate (NMDA) receptor, the intracellular Ca2+, and the intranuclear Ca(2+)-dependent mechanisms. In addition to the developmental status of these cellular components, the response of these potential mechanisms to hypoxia determines the fate of the hypoxic brain cell in the developing brain. Using electron spin resonance spectroscopy of alpha-phenyl-N-tert-butyl-nitrone spin adducts, studies from our laboratory demonstrated that tissue hypoxia results in increased free radical generation in the cortex of fetal guinea pigs and newborn piglets. Pretreatment with MgSO4 significantly decreased the hypoxia-induced increase in free radical generation in the term fetal brain. We also showed that brain tissue hypoxia modifies the NMDA receptor ion-channel recognition and modulatory sites. Furthermore, a higher increase in NMDA receptor agonist-dependent Ca2+ in synaptosomes was demonstrated. The increase in intracellular Ca2+ may activate several enzymatic pathways such as phospholipase A2 and metabolism of archidonic acid by cyclooxygenase and lipoxygenase, conversion of xanthine dehydrogenase to xanthine oxidase by proteases, and activation of nitric oxide synthase. Using inhibitors of each of these enzymes such as cyclooxygenase (indomethacin), lipoxygenase (nordihydroguaiaretic acid), xanthine oxidase (allopurinol), and nitric oxide synthase (N-nitro-L-arginine), studies have shown that these enzyme reactions result in oxygen free radical generation, membrane peroxidation, and cell membrane dysfunction in the hypoxic brain. Specifically, generation of nitric oxide free radicals during hypoxia may lead to nitration and nitrosylation of specific membrane proteins and receptors, resulting in dysfunction of receptors and enzymes. We conclude that hypoxia-induced modification of the NMDA receptor leading to increased intracellular Ca2+ results in free radical generation and cell injury. We suggest that during hypoxia the increased intracellular Ca2+ may lead to increased intranuclear Ca2+ concentration and alter nuclear events including transcription of specific apoptotic genes and activation of endonucleases, resulting in programmed cell death.
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PMID:Mechanisms of perinatal cerebral injury in fetus and newborn. 1081 2