Advertisement

Journal of Inherited Metabolic Disease

, Volume 33, Supplement 3, pp 159–162 | Cite as

Adenylosuccinate lyase deficiency in a Malaysian patient, with novel adenylosuccinate lyase gene mutations

  • Bee Chin Chen
  • Ivan N. McGown
  • Meow Keong Thong
  • James Pitt
  • Zabedah M. Yunus
  • Teck Beng Khoo
  • Lock Hock Ngu
  • John A. Duley
Case Report

Abstract

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).

Keywords

High Performance Liquid Chromatography AICAR Plasma Amino Acid Myoclonic Jerk Severe Psychomotor Retardation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

ADSL

adenylosuccinate lyase

S-Ado

succinyl-adenosine

SAICAr

succinyl-aminoimidazole carboximide riboside

HPLC

high performance liquid chromatography

MS/MS

tandem mass spectrometry

Notes

Acknowledgements

This work was supported by grants from Research and Development, Ministry of Health, Malaysia ( MRG-2006-35).

References

  1. Ariyananda L de Z, Lee P, Antonopoulos C, Colman RF (2009) Biochemical and biophysical analysis of five disease-associated human adenylosuccinate lyase mutants. Biochemistry 48:5291–5302CrossRefGoogle Scholar
  2. Chen BC (2008) Biochemical profiling of hereditary disorders of purine and pyrimidine metabolism. MSc thesis, University of Malaya, Kuala LumpurGoogle Scholar
  3. de Bree PK, Wadman SK, Duran M, de Fabery JH (1986) Diagnosis of inherited adenylosuccinase deficiency by thin-layer chromatography of urinary imidazoles and by automated cation exchange column chromatography of purines. Clin Chim Acta 156:279–287PubMedCrossRefGoogle Scholar
  4. Gitiaux C, Ceballos-Picot I, Marie S, Valayannopoulos V, Rio M, Verrieres S, Benoit JF, Vincent MF, Desguerre I, Bahi-Buisson N (2009) Misleading behavioural phenotype with adenylosuccinate lyase deficiency. Eur J Hum Genet 17:133–136PubMedCrossRefGoogle Scholar
  5. Jaeken J, Van den Berghe G (1984) An infantile autistic syndrome characterised by the presence of succinylpurines in body fluids. Lancet 2:1058–1061PubMedGoogle Scholar
  6. 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
  7. 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
  8. Krijt J, Kmoch S, Hartmannová H, Havlícek V, Sebesta I (1999) Identification and determination of succinyladenosine in human cerebrospinal fluid. J Chromatogr B Biomed Sci Appl 726:53–58PubMedCrossRefGoogle Scholar
  9. 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
  10. Marie S, Race V, Vincent MF, Van den Berghe G (2000) Adenylosuccinate lyase deficiency: from the clinics to molecular biology. Adv Exp Med Biol 486:79–82PubMedCrossRefGoogle Scholar
  11. Marie S, Race V, Nassogne MC, Vincent MF, Van den Berghe G (2002) Mutation of a nuclear respiratory factor 2 binding site in the 5′ untranslated region of the ADSL gene in three patients with adenylosuccinate lyase deficiency. Am J Hum Genet 71:14–21PubMedCrossRefGoogle Scholar
  12. Nyhan WL (2005) Disorders of purine and pyrimidine metabolism. Mol Genet Metab 86:25–33PubMedCrossRefGoogle Scholar
  13. Pitt JJ, Eggington M, Kahler SG (2002) Comprehensive screening of urine samples for inborn errors of metabolism by electrospray tandem mass spectrometry. Clin Chem 48:1970–1980PubMedGoogle Scholar
  14. Sebesta I, Shobowale M, Krijt J, Simmonds HA (1995) Screening tests for adenylosuccinase deficiency. Screening 4:117–124CrossRefGoogle Scholar
  15. Spiegel EK, Colman RF, Patterson D (2006) Adenylosuccinate lyase deficiency. Mol Genet Metab 89:19–31PubMedCrossRefGoogle Scholar
  16. Stone RL, Aimi J, Barshop BA, Jaeken J, Van den Berghe G, Zalkin H, Dixon JE (1992) A mutation in adenylosuccinate lyase associated with mental retardation and autistic features. Nat Genet 1:59–63PubMedCrossRefGoogle Scholar
  17. Stone TW, Roberts LA, Morris BJ, Jones PA, Ogilvy HA, Behan WM, Duley JA, Simmonds HA, Vincent MF, van den Berghe G (1998) Succinylpurines induce neuronal damage in the rat brain. Adv Exp Med Biol 431:185–189PubMedCrossRefGoogle Scholar
  18. 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
  19. Van den Berghe, G. Adenylosuccinate lyase deficiency. Neurology Medlink. http://www.medlink.com/CIP.ASP?UID=MLT002GB accessed 2009
  20. Vidotto C, Fouscrt D, Akkermann M, Griesmacher A, Muller MM (2003) Purine and pyrimidine metabolites in children’s urine. Clin Chim Acta 335:27–32PubMedCrossRefGoogle Scholar

Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • Bee Chin Chen
    • 1
  • Ivan N. McGown
    • 2
  • Meow Keong Thong
    • 3
  • James Pitt
    • 4
  • Zabedah M. Yunus
    • 5
  • Teck Beng Khoo
    • 6
  • Lock Hock Ngu
    • 7
  • John A. Duley
    • 2
    • 8
  1. 1.Biochemical Genetic Unit, Department of GeneticsKuala Lumpur HospitalJalan PahangMalaysia
  2. 2.Pathology DepartmentMater Health ServicesBrisbaneAustralia
  3. 3.Genetic & Metabolism Unit, Dept of Pediatrics, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
  4. 4.The Victorian Clinical Genetics Services (VCGS), PathologyMurdoch Children’s Research InstituteMelbourneAustralia
  5. 5.Division of BiochemistryInstitute for Medical ResearchKuala LumpurMalaysia
  6. 6.Division of Pediatric NeurologyKuala LumpurMalaysia
  7. 7.Division of Clinical Genetics, Department of GeneticsKuala Lumpur HospitalKuala LumpurMalaysia
  8. 8.School of PharmacyThe University of QueenslandBrisbaneAustralia

Personalised recommendations