Clinical, biochemical and molecular findings in seven Polish patients with adenylosuccinate lyase deficiency.
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 Metabolic Diseases, Endocrinology and Diabetology, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.
Agnieszka
A
Jurecka
Institute for Inherited Metabolic Disorders, Ke Karlovu 2, Prague, Czech Republic.
Marie
M
Zikanova
Department of Metabolic Diseases, Endocrinology and Diabetology, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.
Anna
A
Tylki-Szymanska
Institute for Inherited Metabolic Disorders, Ke Karlovu 2, Prague, Czech Republic.
Jakub
J
Krijt
Department of Laboratory Diagnostics, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.
Anna
A
Bogdanska
Department of Laboratory Diagnostics, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.
Wanda
W
Gradowska
Institute for Inherited Metabolic Disorders, Ke Karlovu 2, Prague, Czech Republic.
Karolina
K
Mullerova
Department of Metabolic Diseases, Endocrinology and Diabetology, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.
Jolanta
J
Sykut-Cegielska
Institute for Inherited Metabolic Disorders, Ke Karlovu 2, Prague, Czech Republic.
Stanislav
S
Kmoch
Department of Metabolic Diseases, Endocrinology and Diabetology, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.
Ewa
E
Pronicka
D000264:Adenylosuccinate Lyase / Q000172:deficiency* / Q000235:genetics / Q000652:urine; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D011044:Poland; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics
D000264:Adenylosuccinate Lyase