Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a newborn with exaggerated startle reactions and stiffness of neonatal onset, the prototypical signs of hyperekplexia. Startle and flexor spasms, leading to apnoea, did not respond to treatment with clonazepam but did partially to sodium valproate. Molecular analysis of GLRA1 revealed no mutations. The incidental finding of hypouricemia led to a work-up for molybdenum cofactor (MoCo) deficiency; the diagnosis was confirmed by the altered urine chemistries, including elevated urine S-sulphocysteine. Despite persistence of the spasms, clinical or electrographic seizures were never detected before the infant died at age 1 month. In this patient, the concurrence of hyperekplexia and MoCo deficiency was suggestive of impaired gephyrin function. GPH mutational analysis, however, showed no abnormalities. The patient was eventually found to harbour a novel c.1064T > C mutation in exon 8 of the MOCS1 gene. Despite extensive sequence analysis of the gene, the second causative mutation of this recessive trait still awaits identification. MoCo deficiency should be considered in the differential diagnosis of neonatal hyperekplexia, particularly in the instances of refractoriness to clonazepam, an early demise in infancy or the evidence of no mutations in the GLRA1 gene.
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PMID:Molybdenum cofactor deficiency presenting as neonatal hyperekplexia: a clinical, biochemical and genetic study. 1642 80

Sulfite oxidase is a mitochondrial enzyme encoded by the SUOX gene and essential for the detoxification of sulfite which results mainly from the catabolism of sulfur-containing amino acids. Decreased activity of this enzyme can either be due to mutations in the SUOX gene or secondary to defects in the synthesis of its cofactor, the molybdenum cofactor. Defects in the synthesis of the molybdenum cofactor are caused by mutations in one of the genes MOCS1, MOCS2, MOCS3 and GEPH and result in combined deficiencies of the enzymes sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase. Although present in many ethnic groups, isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are rare inborn errors of metabolism, which makes awareness of key clinical and laboratory features of affected individuals crucial for early diagnosis. We report clinical, radiologic, biochemical and genetic data on a Brazilian and on a Turkish child with sulfite oxidase deficiency due to the isolated defect and impaired synthesis of the molybdenum cofactor, respectively. Both patients presented with early onset seizures and neurological deterioration. They showed no sulfite oxidase activity in fibroblasts and were homozygous for the mutations c.1136A>G in the SUOX gene and c.667insCGA in the MOCS1 gene, respectively. Widely available routine laboratory tests such as assessment of total homocysteine and uric acid are indicated in children with a clinical presentation resembling that of hypoxic ischemic encephalopathy and may help in obtaining a tentative diagnosis locally, which requires confirmation by specialized laboratories.
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PMID:Functional deficiencies of sulfite oxidase: Differential diagnoses in neonates presenting with intractable seizures and cystic encephalomalacia. 1979 32

Molybdenum cofactor (MoCo) deficiency is a rare autosomal recessive inherited metabolic disorder resulting in the combined deficiency of aldehyde oxidase, xanthine dehydrogenase, and sulfite oxidase. We report a male infant with MoCo deficiency whose clinical findings consisted of microcephaly, intractable seizures soon after birth, feeding difficulties, and developmental delay. Sequencing of MOCS1, MOCS2, and GEPH genes, and single nucleotide polymorphism genotyping array analysis showed, to our knowledge, unusual inheritance of MoCo deficiency/maternal uniparental isodisomy for the first time in the literature. At 10 months of age, he now has microcephaly and developmental delay, and his seizures are controlled with phenobarbital, clonozepam, and vigabatrin therapy.
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PMID:Maternal uniparental isodisomy is responsible for serious molybdenum cofactor deficiency. 2057 77