title: Aminoacylase I deficiency: a novel inborn error of metabolism.
abstract: This is the first report of a patient with aminoacylase I deficiency. High amounts of N-acetylated amino acids were detected by gas chromatography-mass spectrometry in the urine, including the derivatives of serine, glutamic acid, alanine, methionine, glycine, and smaller amounts of threonine, leucine, valine, and isoleucine. NMR spectroscopy confirmed these findings and, in addition, showed the presence of N-acetylglutamine and N-acetylasparagine. In EBV transformed lymphoblasts, aminoacylase I activity was deficient. Loss of activity was due to decreased amounts of aminoacylase I protein. The amount of mRNA for the aminoacylase I was decreased. DNA sequencing of the encoding ACY1 gene showed a homozygous c.1057 C>T transition, predicting a p.Arg353Cys substitution. Both parents were heterozygous for the mutation. The mutation was also detected in 5/161 controls. To exclude the possibility of a genetic polymorphism, protein expression studies were performed showing that the mutant protein had lost catalytic activity.
authors.affiliation: Department of Pediatrics, Division of Neurology and Metabolism, University Hospital, Ghent, Belgium. rudy.vancoster@ugent.be
authors.forename: R N
authors.initials: RN
authors.lastname: Van Coster
authors.forename: E A
authors.initials: EA
authors.lastname: Gerlo
authors.forename: T G
authors.initials: TG
authors.lastname: Giardina
authors.forename: U F
authors.initials: UF
authors.lastname: Engelke
authors.forename: J E
authors.initials: JE
authors.lastname: Smet
authors.forename: C M
authors.initials: CM
authors.lastname: De Praeter
authors.forename: V A
authors.initials: VA
authors.lastname: Meersschaut
authors.forename: L J
authors.initials: LJ
authors.lastname: De Meirleir
authors.forename: S H
authors.initials: SH
authors.lastname: Seneca
authors.forename: B
authors.initials: B
authors.lastname: Devreese
authors.forename: J G
authors.initials: JG
authors.lastname: Leroy
authors.forename: S
authors.initials: S
authors.lastname: Herga
authors.forename: J P
authors.initials: JP
authors.lastname: Perrier
authors.forename: R A
authors.initials: RA
authors.lastname: Wevers
authors.forename: W
authors.initials: W
authors.lastname: Lissens
mesh_terms: D000581:Amidohydrolases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D008661:Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics / Q000652:urine; D009154:Mutation / Q000235:genetics; D010447:Peptide Hydrolases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D001120:Arginine; D010447:Peptide Hydrolases; C038220:acylaminoacyl-peptidase; D000581:Amidohydrolases; C019672:aminoacylase I