title: Intrafamilial variability in the phenotypic expression of adenylosuccinate lyase deficiency: a report on three patients.
abstract: We report on the striking variable expression of adenylosuccinate lyase (ADSL) deficiency in three patients belonging to a family which originates from Portugal. ADSL deficiency is a rare autosomal recessive disorder of the de novo purine synthesis which results in accumulation of succinylpurines in body fluids. As a result, patients may have variable combinations of psychomotor retardation and/or regression, seizures, autistic features and cerebellar vermis hypoplasia. However, intrafamilial variable expression of the phenotype has not been documented to date in this disease and is not commonly observed in metabolic disorders. Here, while the proband had marked psychomotor regression and progressive cerebellar vermis atrophy, the other two affected patients presented mainly autistic features. Mutation analysis of the ADSL gene revealed the presence of a homozygous R426H mutation in this family. Finally, although ADSL deficiency is a rare disorder, this diagnosis should be considered and assessed using a simple urinary screening method for the presence of succinylpurines in any patient with mental retardation of unexplained origin.
authors.affiliation: Département de Pédiatrie, Service de Neurologie, C.H.U. de Bicêtre, 94275 Le Kremlin Bicêtre Cédex, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Edery
authors.forename: Stéphane
authors.initials: S
authors.lastname: Chabrier
authors.forename: Irène
authors.initials: I
authors.lastname: Ceballos-Picot
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marie
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Vincent
authors.forename: Marc
authors.initials: M
authors.lastname: Tardieu
mesh_terms: D000264:Adenylosuccinate Lyase / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000652:urine; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000473:pathology; D003241:Consanguinity; D003337:Corpus Callosum / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D005808:Genes, Recessive; D014644:Genetic Variation / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011859:Radiography; D012263:Ribonucleosides / Q000134:cerebrospinal fluid / Q000652:urine; D013687:Telencephalon / Q000000981:diagnostic imaging / Q000473:pathology
chemical_list: D012263:Ribonucleosides; C043566:succinylaminoimidazole carboxamide riboside; D000620:Aminoimidazole Carboxamide; D000264:Adenylosuccinate Lyase