1. ¹Unité de Neurologie Pédiatrique Département de Pédiatrie Hoôpital Necker Enfants Malades, AP-HP, Université Paris Descartes, Paris, France
2. ²Service de Biochimie Métabolique Hôpital Necker Enfants Malades, AP-HP, Université Paris Descartes, Paris, France
3. ³Université Catholique de Louvain Cliniques Universitaires Saint-Luc, Laboratoire de Maladies Métaboliques, Bruxelles Belgique
4. ⁴Unité de Métabolisme Département de Pédiatrie Hôpital Necker Enfants Malades, AP-HP, Université Paris Descartes, Paris, France
5. ⁵Service de génétique, Departement de Pediatrie Hôpital Necker Enfants Malades, AP-HP, Université Paris Descartes, Paris, France
6. ⁶Hôpital d'Argenteuil Service de Pédiatrie, Paris, France
7. ⁷Service de Biochimie – Hormonologie, Hôpital Robert Debré, AP-HP, Paris, France

Correspondence: Dr N Bahi-Buisson, Pediatric Neurology Hopital Necker Enfants Malades, 149 rue de Sèvres, Paris 75015, France. Tel: +33 1 4219 2699; Fax +33 1 4219 2692; E-mail: nadia.bahi-buisson@nck.aphp.fr

Received 15 April 2008; Revised 17 July 2008; Accepted 27 August 2008; Published online 1 October 2008.

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.