Aminoacylase 1 deficiency associated with autistic behavior.
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.
Tylki-Szymanska
Anna
A
Department of Metabolic Diseases, Endocrinology and Diabetology, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.
Gradowska
Wanda
W
Sommer
Anke
A
Heer
Angelina
A
Walter
Melanie
M
Reinhard
Christina
C
Omran
Heymut
H
Sass
Jörn Oliver
JO
Jurecka
Agnieszka
A
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
D000596:Amino Acids; D015415:Biomarkers; D000581:Amidohydrolases; C019672:aminoacylase I