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.
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Abbreviations
- ADSL:
-
adenylosuccinate lyase
- CMHI:
-
Children’s Memorial Health Institute
- HPLC:
-
high-performance liquid chromatography
- SAdo:
-
succinyladenosine
- SAICAr:
-
succinylaminoimidazole carboxamide riboside
- UA:
-
uric acid
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Acknowledgements
Collaboration with other laboratories was made possible by the support of the grant by the Polish Scientific Research Committee PB 1121/P01/2007/32. The succinylnucleoside measurements and DNA analyses were supported by grant 301/07/0600 grant from the Czech Science Foundation and grant VZ 00064165 from the Czech Ministry of Health. Institutional support was provided by the Ministry of Education of the Czech Republic grants 1M6837805002 and MSM0021620806. The authors are grateful for the contribution of our patients’ families. We thank Ryszard T. Smolenski and Ewa Slominska (Gdansk, Poland) for excellent technical support.
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Communicating editor: Lynette Fairbanks
JIMD Short Report #114 (2008) Online
Competing interests: None declared
References to electronic databases: Adenylosuccinate lyase deficiency: OMIM 103050. Adenylosuccinate lyase: EC 4.3.2.2.
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Jurecka, A., Tylki-Szymanska, A., Zikanova, M. et al. d-Ribose therapy in four Polish patients with adenylosuccinate lyase deficiency: Absence of positive effect. J Inherit Metab Dis 31 (Suppl 2), 329–332 (2008). https://doi.org/10.1007/s10545-008-0904-z
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DOI: https://doi.org/10.1007/s10545-008-0904-z