A dipstick test strip (Sulfistix) showing elevated urinary sulfite concentrations (400 mg/l) was used in diagnosis of molybdenum cofactor deficiency (MCD), an inborn errror of metabolism, in a male infant presenting with convulsions and cerebral dysgenesis at birth and followed for 3 years at the Klinik fur Kinder und Jugendmedizin, St Marlenhospital, Vechta, Germany. He was irritable, tremulous, and had brief, repetitive, generalized tonic-clonic seizures on the first day of life. The EEG showed multifocal epileptic discharges, and a brain ultrasound showed microgyria, agenesis of the corpus callosum, and multicystic leucoencephalopathy. A sister had died at age 3 years after a similar illness, diagnosis undetermined. Serum lactate, pyruvate, and ammonia, urine aminoacid and organic acid concentrations, muscle and nerve biopsies, and the mitochondrial genome were normal. Sulfite oxidase deficiency, a diagnosis considered on the first day, was dismissed following a negative test for sulfite made on urine collected and allowed to stand at room temperature. The test was repeated at 2 years, using freshly collected urine, and sulfites were present in increased concentration. Other characteristic laboratory findings for MCD were also positive: serum and urinary uric acid concentrations, not previously tested, were very low, urinary xanthine excretion was increased, and genetic testing found the patient homozygous for the MCD gene mutation R73W on exon 1. At 3 year follow-up, the child was severely retarded and hypotonic, and had bilateral lens dislocations. [1]

COMMENT. A dipstick urine test (Sulfistix,® Merck), commonly used to measure sulfite in wine, should be included in the routine work-up for persistent neonatal seizures, especially in infants born to consanguineous parents. A fresh urine specimen is essential, since sulfite is rapidly oxidized to sulfate at room temperature, nullifying the test. If sulfites are present, measurements of serum and urine concentrations of uric acid should follow.

Molybdenum cofactor deficiency, with resultant sulfite oxidase and xanthine dehydrogenase deficiencies, is an inherited, autosomal recessive, inborn error of metabolism manifesting with neonatal seizures, opisthotonus, craniofacial dysmorphic features, ectopia lentis, and progressive, usually fatal, neurologic deterioration. Although rare, with a total of approximately 15 cases reported, the diagnosis is probably overlooked or delayed, as in the present case-report. Additional reports, not cited by the author, include an infant showing moderate short-term clinical improvement with a diet low in methionine and supplemented with cysteine. (see Progress in Pediatric Neurology Vol II, PNB Publ, 1994;pp474-476; Ped Neur Briefs August 1998;12:58-59). In the US, sulfite dipsticks (Quantofix, Maehery-Nagel) may be purchased at $20/100 through Gallard-Schlesinger, Tel:516-333-5600.