Prenatal diagnosis in adenylosuccinate lyase deficiency

Adenylosuccinate lyase deficiency, an autosomal recessive inborn error of p urine synthesis, provokes accumulation in body fluids of succinylaminoimida zolecarboxamide riboside and succinyladenosine, the dephosphorylated deriva tives of the two substrates of the enzyme. Most patients display severe psy chomotor retardation, often accompanied by epilepsy and/or autistic feature s, although some are only mildly retarded. About 20 mutations are known. Pr enatal diagnosis was performed twice on chorion villi of the mother of a pr eviously diagnosed patient with a C5T mutation (exon 1) on the maternal all ele, and a C1185A mutation (exon 11) on the paternal allele. Both suppress a Fnu4HI restriction site. In a first fetus, incubation of PCR products gen erated from genomic DNA of exon 1 with Fnu4HI yielded a 113 bp fragment fro m a control and the father's gene, and both a 113 bp and 170 bp fragment fr om the mother, affected sibling and fetus. Incubation of PCR products of ex ons 11-12 with Fnu4HI yielded a 550 bp fragment from a control and the moth er's gene, and a 550 bp and 600 bp fragment from the father, affected sibli ng and fetus. Assay of adenylosuccinate lyase on the aborted fetal liver co nfirmed the enzyme deficiency. A second fetus displayed only the maternal m utation. Copyright (C) 2000 John Wiley & Sons, Ltd.