succinyladenosine and Seizures

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).

Topics: Adenosine; Adenosine Monophosphate; Adenylosuccinate Lyase; Aminoimidazole Carboxamide; Autistic Disorder; Biomarkers; Child Development; Chromatography, High Pressure Liquid; DNA Mutational Analysis; Genetic Predisposition to Disease; Genetic Testing; Heterozygote; Humans; Infant; Infant, Newborn; Malaysia; Male; Mutation; Myoclonus; Phenotype; Predictive Value of Tests; Psychomotor Disorders; Psychomotor Performance; Purine-Pyrimidine Metabolism, Inborn Errors; Ribonucleosides; Seizures; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

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.

Topics: Adenosine; Adenylosuccinate Lyase; Aminoimidazole Carboxamide; Autistic Disorder; Blood Glucose; Child; Child, Preschool; Creatinine; Female; Growth Disorders; Humans; Poland; Purine-Pyrimidine Metabolism, Inborn Errors; Ribonucleosides; Ribose; Seizures; Severity of Illness Index; Treatment Failure; Uric Acid