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.
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References
Jaeken J, Van den Berghe G : An infantile autistic syndrome characterised by the presence of succinylpurines in body fluids. Lancet 1984; 2: 1058–1061.
Van den Berghe G, Vincent MF, Jaeken J : Inborn errors of the purine nucleotide cycle: adenylosuccinase deficiency. J Inherit Metab Dis 1997; 20: 193–202.
Jaeken J, Wadman SK, Duran M et al: Adenylosuccinase deficiency: an inborn error of purine nucleotide synthesis. Eur J Pediatr 1988; 148: 126–131.
van den Bergh FA, Bosschaart AN, Hageman G, Duran M, Tien Poll-The B : Adenylosuccinase deficiency with neonatal onset severe epileptic seizures and sudden death. Neuropediatrics 1998; 29: 51–53.
Mouchegh K, Zikanova M, Hoffmann GF et al: Lethal fetal and early neonatal presentation of adenylosuccinate lyase deficiency: observation of 6 patients in 4 families. J Pediatr 2007; 150: 57.e2–61.e2.
Maaswinkel-Mooij PD, Laan LA, Onkenhout W, Brouwer OF, Jaeken J, Poorthuis BJ : Adenylosuccinase deficiency presenting with epilepsy in early infancy. J Inherit Metab Dis 1997; 20: 606–607.
Sebesta I, Krijt J, Kmoch S, Hartmannova H, Wojda M, Zeman J : Adenylosuccinase deficiency: clinical and biochemical findings in 5 Czech patients. J Inherit Metab Dis 1997; 20: 343–344.
Nassogne M, Henrot B, Aubert G et al: Adenylosuccinase deficiency: an unusual cause of early onset epilepsy associated with acquired microcephaly. Brain Dev 2000; 22: 383–386.
Spiegel EK, Colman RF, Patterson D : Adenylosuccinate lyase deficiency. Mol Genet Metab 2006; 89: 19–31.
Laikind PK, Seegmiller JE, Gruber HE : Detection of 5′-phosphoribosyl-4-(N-succinylcarboxamide)-5-aminoimidazole in urine by use of the Bratton–Marshall reaction: identification of patients deficient in adenylosuccinate lyase activity. Anal Biochem 1986; 156: 81–90.
Van den Bergh F, Vincent MF, Jaeken J, Van den Berghe G : Residual adenylosuccinase activities in fibroblasts of adenylosuccinase-deficient children: parallel deficiency with adenylosuccinate and succinyl-AICAR in profoundly retarded patients and non-parallel deficiency in a mildly retarded girl. J Inherit Metab Dis 1993; 16: 415–424.
Marie S, Race V, Vincent MF, Van den Berghe G : Adenylosuccinate lyase deficiency: from the clinics to molecular biology. Adv Exp Med Biol 2000; 486: 79–82.
Race V, Marie S, Vincent MF, Van den Berghe G : Clinical, biochemical and molecular genetic correlations in adenylosuccinate lyase deficiency. Hum Mol Genet 2000; 9: 2159–2165.
Holder-Espinasse M, Marie S, Bourrouillou G et al: Towards a suggestive facial dysmorphism in adenylosuccinate lyase deficiency? J Med Genet 2002; 39: 440–442.
Williams CA, Beaudet AL, Clayton-Smith J et al: Angelman syndrome 2005: updated consensus for diagnostic criteria. Am J Med Genet A 2006; 140: 413–418.
Barry RJ, Leitner RP, Clarke AR, Einfeld SL : Behavioral aspects of Angelman syndrome: a case control study. Am J Med Genet A 2005; 132: 8–12.
Williams CA, Lossie A, Driscoll D : Angelman syndrome: mimicking conditions and phenotypes. Am J Med Genet 2001; 101: 59–64.
Feinstein C, Singh S : Social phenotypes in neurogenetic syndromes. Child Adolesc Psychiatr Clin N Am 2007; 16: 631–647.
Baumgardner TL, Green KE, Reiss AL : A behavioral neurogenetics approach to developmental disabilities: gene-brain-behavior associations. Curr Opin Neurol 1994; 7: 172–178.
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Gitiaux, C., Ceballos-Picot, I., Marie, S. et al. Misleading behavioural phenotype with adenylosuccinate lyase deficiency. Eur J Hum Genet 17, 133–136 (2009). https://doi.org/10.1038/ejhg.2008.174
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DOI: https://doi.org/10.1038/ejhg.2008.174
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