title: Misleading behavioural phenotype with adenylosuccinate lyase deficiency.
abstract: Adenylosuccinate lyase deficiency is a rare autosomal disorder of de novo purine synthesis, which results in the accumulation of succinylpurines in body fluids. Patients with adenylosuccinate lyase deficiency show a variable combination of mental retardation, epilepsy and autistic features and are usually discovered during screens for unexplained encephalopathy using the Bratton-Marshall assay that reveals the excretion of the succinylaminoimidazolecarboxamide riboside (SAICAr). Here, we report on two sisters aged 11 and 12 years presented with global developmental delay, motor apraxia, severe speech deficits, seizures and behavioural features, which combined excessive laughter, a very happy disposition, hyperactivity, a short attention span, the mouthing of objects, tantrums and stereotyped movements that gave a behavioural profile mimicking Angelman syndrome. Both patients had an increased succinyladenosine/SAICAr ratio of 1.6, and exhibited a novel homozygous missense mutation (c.674T>C; p.Met225Thr) in the exon 6 of the ADSL gene. We suggest that these clinical features might be a new presentation of adenylosuccinate lyase deficiency. On the basis of this observation, although adenylosuccinate lyase deficiency is a rare disorder, this diagnosis should be considered in patients with mental retardation and a behavioural profile suggestive of Angelman syndrome.
authors.affiliation: Département de Pédiatrie, Hoôpital Necker Enfants Malades, AP-HP, Université Paris Descartes, Paris, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Gitiaux
authors.forename: Irène
authors.initials: I
authors.lastname: Ceballos-Picot
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marie
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.forename: Marlène
authors.initials: M
authors.lastname: Rio
authors.forename: Séverine
authors.initials: S
authors.lastname: Verrieres
authors.forename: Jean François
authors.initials: JF
authors.lastname: Benoist
authors.forename: Marie Françoise
authors.initials: MF
authors.lastname: Vincent
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desguerre
authors.forename: Nadia
authors.initials: N
authors.lastname: Bahi-Buisson
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000652:urine; D000264:Adenylosuccinate Lyase / Q000172:deficiency* / Q000235:genetics*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000652:urine; D017204:Angelman Syndrome / Q000175:diagnosis; D001519:Behavior; D002648:Child; D002851:Chromatography, High Pressure Liquid; D003241:Consanguinity; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000523:psychology; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D012265:Ribonucleotides / Q000652:urine; D017422:Sequence Analysis, DNA; D013239:Stereotyped Behavior
chemical_list: D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; C043565:succinyladenosine; D000264:Adenylosuccinate Lyase; C020635:SAICAR; D000241:Adenosine