Abstract
Aminoacylase 1 (ACY1) deficiency is a rare inborn error of metabolism presenting with heterogeneous neurological symptoms such as psychomotor delay, seizures, intellectual disability and it is characterized by increased urinary excretion of N-acetylated amino acids. We report on a new patient who presented ACY1 deficiency in association with isolated mild intellectual disability, but neither neurological symptoms nor autistic features. The child showed a compound heterozygous mutation (p.Glu233Asp) and a novel p.Ser192Arg fs*64, predicting an unstable transcript and resulting in very low protein levels.
This new ACY1 deficient child was identified through regular screening for inborn error of metabolism adopted in our department in all cases of intellectual disability. This report supports a recommendation to perform metabolic investigations in patients with isolated mild intellectual disability.
Competing interests: None declared
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References
Chilosi AM, Cipriani P (1996) In: Edizioni del Cerro. TCGB: Test di comprensione grammaticale per bambini. Tirrenia, Pisa
Cook RM, Burke BJ, Buchhagen DL, Minna JD, Miller YE (1993) Human aminoacylase-1: cloning, sequence, and expression analysis of a chromosome 3p21 gene inactivated in small cell lung cancer. J Biol Chem 268:17010–17017
Dunn LM, Dunn LM. (1997) Peabody picture vocabulary test-PPVT, 3rd edn. Minneapolis (MN). American Guidance Service. Italian adaptation; Stella G, Pizzoli C, Tressoldi P (2000) PPVT-revised. Torino: Omega Edition
Engelke UF, Sass JO, Van Coster RN et al (2008) NMR spectroscopy of aminoacylase 1 deficiency, a novel inborn error of metabolism. NMR Biomed 21:138–147
Ferri L, Funghini S, Fioravanti A et al (2013) Aminoacylase I deficiency due to ACY1 mRNA exon skipping. Clin Gen. doi:10.1111/cge.12297
Fiorillo C, Moro F, Brisca G et al (2012) TRPV4 mutations in children with congenital distal spinal muscular atrophy. Neurogenetics Aug 13(3):195–203
Gerlo E, Van Coster R, Lissens W, Winckelmans G, De Meirleir L, Wevers R (2006) Gas chromatographic–mass spectrometric analysis of N-acetylated amino acids: the first case of aminoacylase I deficiency. Anal Chim Acta 571:191–199
Gugliotta M, Bisiacchi PS, Cendron M, Tressoldi PE, Vio C (2009) BVN 12-18-Batteria per la Valutazione Neuropsicologica per l'adolescenza. Edizioni Erickson, Gardolo
Lindner HA, Täfler-Naumann M, Röhm KH (2008) N-acetylamino acid utilization by kidney aminoacylase-1. Biochimie 90:773–780
Lowry OH, Rosebrough NJ, Al F, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Maceyka M, Nava VE, Milstien S, Spiegel S (2004) Aminoacylase 1 is a sphingosine kinase 1-interacting protein. FEBS Lett 568:30–34
Miller YE, Drabkin H, Jones C, Fisher JH (1990) Human aminoacylase-1: cloning, regional assignment to distal chromosome 3p21.1, and identification of a cross-hybridizing sequence on chromosome 18. Genomics 8:149–154
Naylor SL, Shows TB, Klebe RJ (1979) Bioautographic visualization of aminoacylase-1: assignment of the structural gene ACY-1 to chromosome 3 in man. Somat Cell Genet 5:11–21
Naylor SL, Elliott RW, Brown JA, Shows TB (1982) Mapping of aminoacylase- 1 and beta-galactosidase-A to homologous regions of human chromosome 3 and mouse chromosome 9 suggests location of additional genes. Am J Hum Genet 34:235–244
Nogueira C, Barros J, Sá MJ, Azevedo L et al (2013) Novel TTC19 mutation in a family with severe psychiatric manifestations and complex III deficiency. Neurogenetics 14:153–160
Sass JO, Mohr V, Olbrich H et al (2006) Mutations in ACY1, the gene encoding Aminoacylase 1, cause a novel inborn error of metabolism. Am J Hum Genet 78:401–409
Sass JO, Olbrich H, Mohr V et al (2007) Neurological findings in aminoacylase 1 deficiency. Neurology 68:2151–2153
Smith T, Said Ghandour M, Wood PL (2011) Detection of N-acetyl methionine in human and murine brain and neuronal and glial derived cell lines. J Neurochem 118:187–194
Sommer A, Christensen E, Schwenger S et al (2011) The molecular basis of aminoacylase 1 deficiency. Biochim Biophys Acta 1812:685–690
Tanaka K, West-Dull A, Hine DG, Lynn TB, Lowe T (1980) Gas-chromatographic method of analysis for urinary organic acids. II. Description of the procedure, and its application to diagnosis of patients with organic acidurias. Clin Chem 26:1847–1853
Tylki-Szymanska A, Gradowska W, Sommer A et al (2010) Aminoacylase 1 deficiency associated with autistic behavior. J Inherit Metab Dis 33(Suppl 3):S211–S214
Van Coster RN, Gerlo EA, Giardina TG et al (2005) Aminoacylase I deficiency: a novel inborn error of metabolism. Biochem Biophys Res Commun 338:1322–1326
Wechsler D (2003) In: Wechsler intelligence scale for children, 4th edn. Pearson Education Inc., San Antonio
Zabel C, Sagi D, Kaindl AM, Steireif N et al (2006) Comparative proteomics in neurodegenerative and non-neurodegenerative diseases suggest nodal point proteins in regulatory networking. J Proteome Res 5:1948–1958
Acknowledgments
The authors thank Dr. Filippo M. Santorelli for his important suggestions and Mrs. Rita Magni for excellent technical assistance.
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Communicated by: Francois Feillet, MD, PhD
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Concise 1 Sentence Take-Home Message
The isolated mild intellectual disability in a child harboring two mutations in ACY1 recommends thorough metabolic investigations in patients affected by intellectual disability of unknown origin.
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Maria G Alessandrì, Manuela Casarano, Ilaria Pezzini, Stefano Doccini, Claudia Nesti, Giovanni Cioni, and Roberta Battini declare that they have no conflict of interest.
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All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with Helsinki Declaration of 1975, as revised in 2000. Parents of the proband gave their informed consent to participate in the study.
Contributions of Individual Authors
Maria G Alessandrì: biochemical analyses, concept and drafting of manuscript. Manuela Casarano, Roberta Battini: clinical data and drafting of manuscript. Ilaria Pezzini: performed mutation analysis. Stefano Doccini: performed protein and cellular studies. Claudia Nesti: directed molecular genetic studies. Giovanni Cioni: design and revision of manuscript.
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Alessandrì, M.G. et al. (2014). Isolated Mild Intellectual Disability Expands the Aminoacylase 1 Phenotype Spectrum. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports Volume 16. JIMD Reports, vol 16. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_323
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DOI: https://doi.org/10.1007/8904_2014_323
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