BACKGROUND: Aminoacylase 1 (ACY1, EC 3.5.1.14) deficiency (ACY1D) is a very rare inherited metabolic disease (IMD) with autosomal recessive inheritance (OMIM #609924). Up to date, only 15 cases have been reported in the literature. It is diagnosed by detecting acetylated amino acids among the patient's urine organic acids by gas chromatography-mass spectrometry. Its clinical manifestations are highly variable, ranging from severe neurological symptoms to being asymptomatic. CASE DESCRIPTION: We present a 14-year-old boy with mild intellectual disability, speech sound disorder and non-alcoholic fatty liver disease who exhibited increased urinary excretion of N-acetylalanine, N-acetylmethionine and N-acetylglutamine during testing for inherited metabolic disorders. A suspected ACY1D was subsequently confirmed by targeted next generation sequencing, which revealed the presence of a homozygous pathogenic missense mutation in the ACY1 gene, c.1057C>T (p.Arg353Cys). The proband underwent speech education with good outcome. The same homozygous mutation in ACY1 gene was found in the boy's two brothers, who exhibited slightly varied intellectual abilities. Follow-up examinations of the siblings revealed no deterioration in their mental skills. CONCLUSIONS: These results suggest that uneven mental abilities in pediatric patients with various disorders including autism spectrum disorder may be sufficient grounds to warrant metabolic testing for ACY1D. The acylglycines urine excretion could be a promising novel metabolic marker for ACY1D testing.

Cancer Research Czech Republic Olomouc Olomouc Czech Republic

Department of Clinical Psychology University Hospital Olomouc Olomouc Czech Republic

Department of Paediatrics University Hospital Olomouc Olomouc Czech Republic

Institute of Medical Genetics University Hospital Olomouc Olomouc Czech Republic

Laboratory for Inherited Metabolic Disorders Department of Clinical Biochemistry University Hospital Olomouc Olomouc Czech Republic

Laboratory of Experimental Medicine Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Czech Advanced Technology and Research Institute Palacky University Olomouc Olomouc Czech Republic

Zobrazit více v PubMed

Tock L, Prado WL, Caranti DA, et al. Nonalcoholic fatty liver disease decrease in obese adolescents after multidisciplinary therapy. Eur J Gastroenterol Hepatol 2006;18:1241-5. 10.1097/01.meg.0000243872.86949.95 PubMed DOI

Van Coster RN, Gerlo EA, Giardina TG, et al. Aminoacylase I deficiency: a novel inborn error of metabolism. Biochem Biophys Res Commun 2005;338:1322-6. 10.1016/j.bbrc.2005.10.126 PubMed DOI

Khalil YA, Rabès JP, Boileau C, et al. APOE gene variants in primary dyslipidemia. Atherosclerosis 2021;328:11-22. 10.1016/j.atherosclerosis.2021.05.007 PubMed DOI

Sass JO, Vaithilingam J, Gemperle-Britschgi C, et al. Expanding the phenotype in aminoacylase 1 (ACY1) deficiency: characterization of the molecular defect in a 63-year-old woman with generalized dystonia. Metab Brain Dis 2016;31:587-92. 10.1007/s11011-015-9778-6 PubMed DOI

Sommer A, Christensen E, Schwenger S, et al. The molecular basis of aminoacylase 1 deficiency. Biochim Biophys Acta 2011;1812:685-90. 10.1016/j.bbadis.2011.03.005 PubMed DOI

Sass JO, Olbrich H, Mohr V, et al. Neurological findings in aminoacylase 1 deficiency. Neurology 2007;68:2151-3. 10.1212/01.wnl.0000264933.56204.e8 PubMed DOI

Sass JO, Mohr V, Olbrich H, et al. Mutations in ACY1, the gene encoding aminoacylase 1, cause a novel inborn error of metabolism. Am J Hum Genet 2006;78:401-9. 10.1086/500563 PubMed DOI PMC

Alessandrì MG, Casarano M, Pezzini I, et al. Isolated Mild Intellectual Disability Expands the Aminoacylase 1 Phenotype Spectrum. In: Zschocke J, Gibson K, Brown G, et al. editors. JIMD Reports Volume 16. Berlin, Heidelberg: Springer; 2014:81-7. PubMed PMC

Ferri L, Funghini S, Fioravanti A, et al. Aminoacylase I deficiency due to ACY1 mRNA exon skipping. Clin Genet 2014;86:367-72. 10.1111/cge.12297 PubMed DOI

Tylki-Szymanska A, Gradowska W, Sommer A, et al. Aminoacylase 1 deficiency associated with autistic behavior. J Inherit Metab Dis 2010;33 Suppl 3:S211-4. 10.1007/s10545-010-9089-3 PubMed DOI

Alessandrì MG, Milone R, Casalini C, et al. Four years follow up of ACY1 deficient patient and pedigree study. Brain Dev 2018;40:570-5. 10.1016/j.braindev.2018.03.009 PubMed DOI