Adenylosuccinate lyase (ADSL) catalyzes two steps in purine nucleotide metabolism-the 8th step in the de novo pathway: conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazole carboxamide ribotide (AICAR), and conversion of adenylosuccinate (S-AMP) to adenylate (AMP) in the purine nucleotide cycle. To date, over 50 patients have been reported suffering from ADSL deficiency. We report all seven so far diagnosed Polish patients with this defect. Most of our patients shared intractable seizures and psychomotor retardation since the neonatal period and had biochemical evidence of severe (type I) deficiency. Two patients with type II suffered only from mild/moderate psychomotor retardation and showed a transientvisual contact disturbance. One patient had a fatal neonatal form of ADSL deficiency with lack of spontaneous movement, respiratory failure, severe encephalopathy and intractable seizures. Analysis of the ADSL gene showed that four apparently unrelated patients carried a R426H mutation (two homozygous and two compound heterozygous). With the exception of the latter mutation, a Y114H mutation that had been reported previously, and a novel mutation T242I, all other mutations (including D268H and three novel S23R, D215H and I351T mutations) were found only in single families in single alleles. A search for this disorder should be included in the screening program of all infants with unexplained neonatal seizures, severe infantile epileptic encephalopathy, developmental delay, hypotonia, and/or autistic features.

Department of Laboratory Diagnostics The Children's Memorial Health Institute Al Dzieci Polskich 20 04 730 Warsaw Poland

Department of Metabolic Diseases Endocrinology and Diabetology The Children's Memorial Health Institute Al Dzieci Polskich 20 04 730 Warsaw Poland

Institute for Inherited Metabolic Disorders Ke Karlovu 2 Prague Czech Republic

References provided by Crossref.org

Combined Targeted and Untargeted Profiling of HeLa Cells Deficient in Purine De Novo Synthesis

Pathway-specific effects of ADSL deficiency on neurodevelopment

Genetic and metabolomic analysis of AdeD and AdeI mutants of de novo purine biosynthesis: cellular models of de novo purine biosynthesis deficiency disorders