Journal of Inherited Metabolic Disease

, Volume 31, Supplement 2, pp 329–332

d-Ribose therapy in four Polish patients with adenylosuccinate lyase deficiency: Absence of positive effect

  • A. Jurecka
  • A. Tylki-Szymanska
  • M. Zikanova
  • J. Krijt
  • S. Kmoch
Short Report

Summary

Deficiency of adenylosuccinate lyase (ADSL) (OMIM 103050) is an autosomal recessive disorder of the purine de novo synthesis pathway and purine nucleotide cycle, diagnosed so far in approximately 50 patients. The clinical presentation is characterized by severe neurological involvement including hypotonia, seizures, developmental delay and autistic features. Epilepsy in ADSL deficiency is frequent and occurs in approximately two-thirds of patients, beginning either early in the neonatal period or after the first year of life. At present there is no treatment of proven clinical efficacy. Despite of the increasing number of ADSL-deficient patients reported, there are only a few communications of therapeutic considerations or efforts. Among them only two showed some beneficial effects in ADSL-deficient patients. d-Ribose, a simple and relatively cheap therapy, has been associated with improvement of behaviour and progressive reduction of the seizure frequency in one 13-year-old patient with ADSL deficiency. In this study we have re-examined d-ribose treatment in four ADSL-deficient patients. Assessments consisted of biochemical markers and neurological outcome. The 12-month trial of d-ribose failed to show any clinical benefit in ADSL patients with both milder and severe phenotype. d-Ribose administration was accompanied by neither reduction in seizure frequency nor growth enhancement. Additionally, patients with milder type II presented the first seizure after 4 and 8 months of the d-ribose treatment. Therefore, we could not confirm a positive effect of d-ribose as previously reported.

Abbreviations

ADSL

adenylosuccinate lyase

CMHI

Children’s Memorial Health Institute

HPLC

high-performance liquid chromatography

SAdo

succinyladenosine

SAICAr

succinylaminoimidazole carboxamide riboside

UA

uric acid

References

  1. Castro M, Perez-Cerda C, Merinero B, et al (2002) Screening for adenylosuccinate lyase deficiency: clinical, biochemical and molecular findings in four patients. Neuropediatrics 33(4): 186–189.PubMedCrossRefGoogle Scholar
  2. Ciardo F, Salerno C, Curatolo P (2001) Neurologic aspects of adenylosuccinate lyase deficiency. J Child Neurol 16(5): 301–308.PubMedGoogle Scholar
  3. Greenwood MC, Dillon MJ, Simmonds HA, et al (1982) Renal failure due to 2,8-dihydrohyadenine urolithiasis. Eur J Pediatr 138(4): 346–349.PubMedCrossRefGoogle Scholar
  4. Jaeken J, Van den Berghe G (1984) An infantile autistic syndrome characterised by the presence of succinylpurines in body fluids. Lancet 2(8411): 1058–1061.PubMedGoogle Scholar
  5. Jaeken J, Wadman SK, Duran M, et al (1988) Adenylosuccinase deficiency: An inborn error of purine nucleotide synthesis. Eur J Pediatr 148: 126–131.PubMedCrossRefGoogle Scholar
  6. Jurecka A, Zikanova M, Tylki-Szymanska A, et al (2008) Clinical, biochemical and molecular findings in seven Polish patients with adenylosuccinate lyase deficiency. Mol Genet Metab, doi:10.1016/j.mgme.2008.04.013.Google Scholar
  7. Krijt J, Kmoch S, Sebesta I, et al (1999) Identification and determination of succinyladenosine in human cerebrospinal fluid. J Chromatogr B Biomed Sci Appl 726: 53–58.PubMedCrossRefGoogle Scholar
  8. Marinaki AM, Champion M, Kurian MA, et al (2004) Adenylosuccinate lyase deficiency – first British case. Nucleosides Nucleotides Nucleic Acids 23(8–9): 1399–1401.PubMedCrossRefGoogle Scholar
  9. Mouchegh K, Zikánová M, Hoffmann GF, et al (2007) Lethal fetal and early neonatal presentation of adenylosuccinate lyase deficiency: observation of 6 patients in 4 families. J Pediatr 150(1): 57–61 e2.PubMedCrossRefGoogle Scholar
  10. Salerno C, Celli M, Finocchiaro R, et al (1998) Effect of d-ribose administration to a patient with inherited deficit of adenylosuccinase. Adv Exp Med Biol 431: 177–180.PubMedGoogle Scholar
  11. Salerno C, Crifo C, Curatolo P, Ciardo F (2000) Effect of uridine administration to a patient with adenylosuccinate lyase deficiency. Adv Exp Med Biol 486: 75–78.PubMedCrossRefGoogle Scholar
  12. Segal S, Foley J (1958) The metabolism of d-ribose in man. J Clin Invest 37(5): 719–735.PubMedCrossRefGoogle Scholar
  13. Spiegel EK, Colman RF, Patterson D (2006) Adenylosuccinate lyase deficiency. Mol Genet Metab 89(1–2):19–31.PubMedCrossRefGoogle Scholar
  14. Stathis SL, Cowley DM, Broe D (2000) Autism and adenylosuccinase deficiency. J Am Acad Child Adolesc Psychiatry 39(3): 274–275.PubMedCrossRefGoogle Scholar
  15. Stone TW, Roberts LA, Morris BJ, et al (1998) Succinylpurines induce neuronal damage in the rat brain. Adv Exp Med Biol 431: 185–189.PubMedGoogle Scholar
  16. Tullson PC, Terjung RL (1991) Adenine nucleotide synthesis in exercising and endurance-trained skeletal muscle. Am J Physiol 261 (2 Pt 1): C342–C347.PubMedGoogle Scholar
  17. Van den Bergh FA, Bosschaart AN, Hageman G, et al (1998) Adenylosuccinase deficiency with neonatal onset, severe epileptic seizures and sudden death. Neuropediatrics 29: 51–53.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • A. Jurecka
    • 1
  • A. Tylki-Szymanska
    • 1
  • M. Zikanova
    • 2
  • J. Krijt
    • 2
  • S. Kmoch
    • 2
  1. 1.Department of Metabolic Diseases, Endocrinology and DiabetologyThe Children’s Memorial Health InstituteWarsawPoland
  2. 2.Institute for Inherited Metabolic DisordersCharles University, 1st Faculty of MedicinePragueCzech Republic

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