title: In vivo proton MR spectroscopy findings specific for adenylosuccinate lyase deficiency.
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.
authors.affiliation: Department of Pediatrics and Pediatric Neurology, Georg August University, Göttingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Henneke
authors.forename: S
authors.initials: S
authors.lastname: Dreha-Kulaczewski
authors.forename: K
authors.initials: K
authors.lastname: Brockmann
authors.forename: M
authors.initials: M
authors.lastname: van der Graaf
authors.forename: M A A P
authors.initials: MA
authors.lastname: Willemsen
authors.forename: U
authors.initials: U
authors.lastname: Engelke
authors.forename: P
authors.initials: P
authors.lastname: Dechent
authors.forename: A
authors.initials: A
authors.lastname: Heerschap
authors.forename: G
authors.initials: G
authors.lastname: Helms
authors.forename: R A
authors.initials: RA
authors.lastname: Wevers
authors.forename: J
authors.initials: J
authors.lastname: Gärtner
mesh_terms: D000264:Adenylosuccinate Lyase / Q000172:deficiency*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid / Q000652:urine; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011522:Protons; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000201:enzymology* / Q000652:urine; D012265:Ribonucleotides / Q000134:cerebrospinal fluid / Q000652:urine; D012436:S-Adenosylmethionine / Q000134:cerebrospinal fluid / Q000652:urine
chemical_list: D011522:Protons; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D012436:S-Adenosylmethionine; D000264:Adenylosuccinate Lyase; C020635:SAICAR