ABSTRACT
Adenylosuccinate lyase (ADSL) deficiency is an inherited metabolic disorder affecting predominantly the central nervous system. The disease is characterized by the accumulation of succinylaminoimidazolecarboxamide riboside and succinyladenosine (S-Ado) in tissue and body fluids. Three children presented with muscular hypotonia, psychomotor delay, behavioral abnormalities, and white matter changes on brain MRI. Two of them were affected by seizures. Screening for inborn errors of metabolism including in vitro high resolution proton MRS revealed an ADSL deficiency that was confirmed genetically in all cases. All patients were studied by in vivo proton MRS. In vitro high resolution proton MRS of patient cerebrospinal fluid showed singlet resonances at 8.27 and 8.29 ppm that correspond to accumulated S-Ado. In vivo proton MRS measurements also revealed a prominent signal at 8.3 ppm in gray and white matter brain regions of all patients. The resonance was undetectable in healthy human brain. In vivo proton MRS provides a conclusive finding in ADSL deficiency and represents a reliable noninvasive diagnostic tool for this neurometabolic disorder.
Subject(s)
Adenylosuccinate Lyase/deficiency , Protons , Purine-Pyrimidine Metabolism, Inborn Errors/diagnosis , Purine-Pyrimidine Metabolism, Inborn Errors/enzymology , Aminoimidazole Carboxamide/analogs & derivatives , Aminoimidazole Carboxamide/cerebrospinal fluid , Aminoimidazole Carboxamide/urine , Child , Child, Preschool , Female , Humans , Hydrogen-Ion Concentration , Infant , Infant, Newborn , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Male , Purine-Pyrimidine Metabolism, Inborn Errors/cerebrospinal fluid , Purine-Pyrimidine Metabolism, Inborn Errors/urine , Ribonucleotides/cerebrospinal fluid , Ribonucleotides/urine , S-Adenosylmethionine/cerebrospinal fluid , S-Adenosylmethionine/urineABSTRACT
A deficiency of adenylosuccinate lyase (ASDL) is characterised by the accumulation of SAICAriboside (SAICAr) and succinyladenosine (S-Ado) in body fluids. The severity of the clinical presentation correlates with a low S-Ado/SAICAr ratio in body fluids. We report the first British case of ADSL deficiency. The patient presented at 14 days with a progressive neonatal encephalopathy and seizures. There was marked axial and peripheral hypotonia. Brain MRI showed widespread white matter changes. She died at 4 weeks of age. Concentrations of SAICAr and SAdo were markedly elevated in urine, plasma and CSF and the SAdo/SAICAr ratio was low, consistent with the severe phenotype. The patient was compound heterozygous for 2 novel ADSL mutations; c.9 G>C (A3P) and c.572 C>T (R190X).