Clinical and laboratory barriers to the timely diagnosis of sulphite oxidase deficiency

Abstract

Isolated sulphite oxidase deficiency (SOD) is a rare genetic neurometabolic disorder characterised by intractable seizures and progressive severe neurological dysfunction. Affected children commonly present at or soon after birth with seizures and neurological deficits. In the newborn period, diagnosis may be missed as clinical features may mimic perinatal hypoxia-ischaemia, a more common entity. We report an infant with SOD whose clinical presentation of seizures and lethargy on the 4th day of life had suggested hypoxic-ischaemic encephalopathy, and discuss the challenges in the diagnostic process. The infant's progressive severe neurological deterioration suggested a metabolic disorder. His brain magnetic resonance imaging at 10 weeks showed severe cerebral atrophy and cystic changes. Biochemical findings of a very low plasma cystine concentration (<5μmol/L, reference range 24-100) and elevated urinary sulphocysteine in the presence of a normal plasma uric acid pointed towards SOD. The diagnosis was confirmed by mutational analysis. Isolated SOD can be difficult to diagnose on the basis of clinical features and routine metabolic tests. Nonetheless heightened awareness of the SOD entity coupled with selective biochemical testing will help towards a more accurate diagnosis. The disorder should be considered in all infants with unexplained hypoxic-ischaemic encephalopathy or progressive neurological dysfunction.