Adenylosuccinase deficiency: possibly underdiagnosed encephalopathy with variable clinical features

Adenylosuccinase deficiency is an autosomal recessive inherited defect of purine synthesis. In enzyme deficient patients, two normally undetectable compounds, succinylaminoimidazole carboxamide riboside and succinyladenosine, accumulate in urine, cerebrospinal fluid and, to a minor extent, in plasma. Analysing 150 highly selected urine specimens from patients with unidentified neurogenerative disorders we discovered the first two German cases of adenylosuccinase deficiency. The deficiency causes moderate to severe mental retardation, often accompanied by epileptic seizures and/or autistic features, and is occasionally associated with growth retardation and muscular hypotonia. Of the two German cases we present here, one patient fits into the clinical picture outlined by previous reports. The other patient, however, shows a pattern of symptoms so far undescribed: severe early infantile epileptic encephalopathy with reduced myelination. On mutation analysis this patient is the first to reveal a 39 base pair deletion in the adenylosuccinase gene in contrast to the point mutations detected in previous cases. Adenylosuccinase deficiency may be an underdiagnosed metabolic disorder with variable expression. This should be taken into consideration in patients with unclassified neurological conditions.