title: Aminoacylase 1 deficiency associated with autistic behavior.
abstract: Aminoacylase 1 (ACY1) deficiency is a recently described inborn error of metabolism. Most of the patients reported so far have presented with rather heterogeneous neurologic symptoms. At this moment, it is not clear whether ACY1 deficiency represents a true metabolic disease with a causal relationship between the enzyme defect and the clinical phenotype or merely a biochemical abnormality. Here we present a patient identified in the course of selective screening for inborn errors of metabolism (IEM). The patient was diagnosed with autistic syndrome and admitted to the Children's Memorial Health Institute (CMHI) for metabolic evaluation. Organic acid analysis using gas chromatography-mass spectrometry (GC-MS) revealed increased urinary excretion of several N-acetylated amino acids, including the derivatives of methionine, glutamic acid, alanine, glycine, leucine, isoleucine, and valine. In Epstein-Barr virus (EBV)-transformed lymphoblasts, ACY1 activity was deficient. The mutation analysis showed a homozygous c.1057C>T transition, predicting a p.Arg353Cys substitution. Both parents were heterozygous for the mutation and had normal results in the organic acid analysis using GC-MS. This article reports the findings of an ACY1-deficient patient presenting with autistic features.
authors.affiliation: Department of Metabolic Diseases, Endocrinology and Diabetology, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Tylki-Szymanska
authors.forename: Wanda
authors.initials: W
authors.lastname: Gradowska
authors.forename: Anke
authors.initials: A
authors.lastname: Sommer
authors.forename: Angelina
authors.initials: A
authors.lastname: Heer
authors.forename: Melanie
authors.initials: M
authors.lastname: Walter
authors.forename: Christina
authors.initials: C
authors.lastname: Reinhard
authors.forename: Heymut
authors.initials: H
authors.lastname: Omran
authors.forename: Jörn Oliver
authors.initials: JO
authors.lastname: Sass
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jurecka
mesh_terms: D000581:Amidohydrolases / Q000172:deficiency* / Q000235:genetics; D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications* / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D000596:Amino Acids / Q000652:urine; D001321:Autistic Disorder / Q000175:diagnosis / Q000209:etiology*; D015415:Biomarkers / Q000652:urine; D002478:Cells, Cultured; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D008401:Gas Chromatography-Mass Spectrometry; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D014162:Transfection
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D000581:Amidohydrolases; C019672:aminoacylase I