molybdenum-cofactor and Spasms--Infantile

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.

Topics: Carbon-Carbon Lyases; Coenzymes; DNA Mutational Analysis; Exons; Humans; Infant; Male; Metalloproteins; Molybdenum Cofactors; Nuclear Proteins; Pteridines; Reflex, Abnormal; Reflex, Startle; Spasm; Spasms, Infantile

Intractable seizures in the neonatal period may be caused by molybdenum-cofactor deficiency, an inborn error which combines the deficiencies of sulphite oxidase and xanthine dehydrogenase. The neurological symptoms of molybdenum cofactor and isolated sulphite oxidase deficiencies are identical. Two new cases are reported, and the literature on neonatal convulsions due to molybdenum-cofactor and sulphite deficiencies is reviewed. Because of the high incidence of neonatal convulsions a search for this deficiency is advocated in each case of unexplained refractory neonatal convulsions. Diagnosis may be missed or delayed on standard metabolic screening for several reasons discussed. By simply using a sulphite strip test in a fresh urine sample an indication for the defect can be obtained. Antenatal diagnosis can be performed by assay of sulphite oxidase activity in a chorionic villus sample.

Topics: Amino Acids; Brain; Brain Diseases; Calcinosis; Chorionic Villi Sampling; Coenzymes; Female; Humans; Infant, Newborn; Male; Metabolic Diseases; Metalloproteins; Molybdenum; Molybdenum Cofactors; Oxidoreductases Acting on Sulfur Group Donors; Pregnancy; Prenatal Diagnosis; Prognosis; Pteridines; Spasms, Infantile; Tomography, X-Ray Computed; Xanthine Dehydrogenase