Novel features in the evolution of adenylosuccinate lyase deficiency

Eur J Paediatr Neurol. 2012 Jul;16(4):343-8. doi: 10.1016/j.ejpn.2011.08.008. Epub 2011 Sep 7.


Background: Adenylosuccinate lyase (ADSL) deficiency is an autosomal recessive disorder of the purine synthesis which results in accumulation of succinylpurines (succinyladenosine (S-Ado) and succinylamino-imidazole carboxamide riboside (SAICAr)) in body fluids. Patients present developmental delay, often accompanied by epilepsy and autistic spectrum disorders.

Objectives: To describe atypical neurological features in the evolution of three novel unrelated cases of ADSL deficiency.

Patients: A 9-year-old boy with severe cognitive impairment and autistic behaviour received d-ribose therapy for one year. Drug withdrawal was associated with acute neurological deterioration, severe brain atrophy and demyelination on MRI. The second patient is a 5.5-year-old girl with mild developmental delay who presented a benign course with moderate cognitive impairment as the only feature in her evolution. The final patient is a 14-year-old boy with severe cognitive impairment who developed drug-resistant epilepsy and bathing reflex seizures, progressive spasticity in the lower limbs and thoracic deformity.

Methods: SAICAr and S-Ado in urine were analysed by HPLC with diode array detection. Diagnosis was confirmed by molecular analysis of the ADSL gene.

Results: An elevation of S-Ado and SAICAr excretion in urine was detected in all three patients. The patients were homozygous for the missence change p.I369L and for the novel change p.M389V.

Conclusion: Drug-resistant epilepsy and specific therapeutic interventions may modify the neurological outcome in ADSL deficiency. d-ribose must be considered with caution as, in our experience, it returns no clinical benefit and drug withdrawal can precipitate status epilepticus and acute neurological deterioration.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylosuccinate Lyase / deficiency*
  • Adenylosuccinate Lyase / genetics
  • Adolescent
  • Autistic Disorder
  • Brain / pathology
  • Child
  • Child Behavior Disorders / etiology
  • Child, Preschool
  • Cognition Disorders / etiology
  • Education, Special
  • Epilepsy / etiology
  • Epilepsy, Reflex / etiology
  • Female
  • Fever / etiology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Movement Disorders / etiology
  • Muscle Spasticity / etiology
  • Neuropsychological Tests
  • Purine-Pyrimidine Metabolism, Inborn Errors / diagnosis
  • Purine-Pyrimidine Metabolism, Inborn Errors / pathology
  • Purine-Pyrimidine Metabolism, Inborn Errors / psychology*
  • Quadriplegia / etiology
  • Ribose / therapeutic use


  • Ribose
  • Adenylosuccinate Lyase

Supplementary concepts

  • Adenylosuccinate lyase deficiency