Adenylosuccinate lyase deficiency in a Malaysian patient, with novel adenylosuccinate lyase gene mutations
- 218 Downloads
Most cases of adenylosuccinate lyase (ADSL OMIM 103050) deficiency reported to date are confined to the various European ethnic groups. We report on the first Malaysian case of ADSL deficiency, which appears also to be the first reported Asian case. The case was diagnosed among a cohort of 450 patients with clinical features of psychomotor retardation, global developmental delay, seizures, microcephaly and/or autistic behaviour. The patient presented with frequent convulsions and severe myoclonic jerk within the first few days of life and severe psychomotor retardation. The high performance liquid chromatography (HPLC) profile of the urine revealed the characteristic biochemical markers of succinyladenosine (S-Ado) and succinyl-aminoimidazole carboximide riboside (SAICAr). The urinary S-Ado/SAICAr ratio was found to be 1.02 (type I ADSL deficiency). The patient was compound heterozygous for two novel mutations, c.445C > G (p.R149G) and c.774_778insG (p.A260GfsX24).
KeywordsHigh Performance Liquid Chromatography AICAR Plasma Amino Acid Myoclonic Jerk Severe Psychomotor Retardation
succinyl-aminoimidazole carboximide riboside
high performance liquid chromatography
tandem mass spectrometry
This work was supported by grants from Research and Development, Ministry of Health, Malaysia ( MRG-2006-35).
- Chen BC (2008) Biochemical profiling of hereditary disorders of purine and pyrimidine metabolism. MSc thesis, University of Malaya, Kuala LumpurGoogle Scholar
- Jurecka A, Zikanova M, Tylki-Szymanska A, Krijt J, Bogdanska A, Gradowska W, Mullerova K, Sykut-Cegielska J, Kmoch S, Pronicka E (2008) Clinical, biochemical and molecular findings in seven Polish patients with adenylosuccinate lyase deficiency. Mol Genet Metab 94:435–442PubMedCrossRefGoogle Scholar
- Kmoch S, Hartmannová H, Stibůrková B, Krijt J, Zikánová M, Sebesta I (2000) Human adenylosuccinate lyase (ADSL), cloning and characterization of full-length cDNA and its isoform, gene structure and molecular basis for ADSL deficiency in six patients. Hum Mol Genet 9:1501–1513PubMedCrossRefGoogle Scholar
- Marie S, Cuppens H, Heuterspreute M, Jaspers M, Tola EZ, Gu XX, Legius E, Vincent MF, Jaeken J, Cassiman JJ, Van den Berghe G (1999) Mutation analysis in adenylosuccinate lyase deficiency: eight novel mutations in the re-evaluated full ADSL coding sequence. Hum Mutat 13:197–202PubMedCrossRefGoogle Scholar
- Van den Berghe G, Jaeken J (2001) Adenylosuccinate lyase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler KW, Vogelstein B (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, New York, pp 2653–2662Google Scholar
- Van den Berghe, G. Adenylosuccinate lyase deficiency. Neurology Medlink. http://www.medlink.com/CIP.ASP?UID=MLT002GB accessed 2009