title: Novel features in the evolution of adenylosuccinate lyase deficiency.
abstract: 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.
  
  
  OBJECTIVE
  To describe atypical neurological features in the evolution of three novel unrelated cases of ADSL deficiency.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Neurology, Hospital Sant Joan de Déu, Passeig Sant Joan de Dèu 2, 08950 Esplugues, Barcelona, Spain. bperez@hsjdbcn.org
authors: Belén
authors: B
authors: Pérez-Dueñas
authors: Angela
authors: A
authors: Sempere
authors: Jaume
authors: J
authors: Campistol
authors: Itziar
authors: I
authors: Alonso-Colmenero
authors: María
authors: M
authors: Díez
authors: Verónica
authors: V
authors: González
authors: Begoña
authors: B
authors: Merinero
authors: Lourdes R
authors: LR
authors: Desviat
authors: Rafael
authors: R
authors: Artuch
mesh_terms: D000264:Adenylosuccinate Lyase / Q000172:deficiency* / Q000235:genetics; D000293:Adolescent; D001321:Autistic Disorder; D001921:Brain / Q000473:pathology; D002648:Child; D002653:Child Behavior Disorders / Q000209:etiology; D002675:Child, Preschool; D003072:Cognition Disorders / Q000209:etiology; D004519:Education, Special; D004827:Epilepsy / Q000209:etiology; D020195:Epilepsy, Reflex / Q000209:etiology; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009069:Movement Disorders / Q000209:etiology; D009128:Muscle Spasticity / Q000209:etiology; D009483:Neuropsychological Tests; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000175:diagnosis / Q000473:pathology / Q000523:psychology*; D011782:Quadriplegia / Q000209:etiology; D012266:Ribose / Q000627:therapeutic use
chemical_list: D012266:Ribose; D000264:Adenylosuccinate Lyase