Aminoacylase 1 deficiency is a rare
inborn error of metabolism
Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances ( substr ...
. To date only 21 cases have been described.
[Ferri L, Funghini S, Fioravanti A, Biondi E, La Marca G, Guerrini R, Donati M, Morrone A (2013) Aminoacylase I deficiency due to ACY1 mRNA exon skipping. Clin Genet doi: 10.1111/cge.12297 ][Sass JO, Mohr V, Olbrich H, Engelke U, Horvath J, Fliegauf M, Loges NT, Schweitzer-Krantz S, Moebus R, Weiler P, Kispert A, Superti-Furga A, Wevers RA, Omran H (2006) Mutations in ACY1, the gene encoding aminoacylase 1, cause a novel inborn error of metabolism. Am J Hum Genet 78(3):401-409]
Signs and symptoms
The clinical picture is heterogeneous and includes motor delay,
seizure
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...
s, moderate to severe mental retardation, absent speech, growth delay, muscular
hypotonia
Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases ...
and
autistic features.
Genetics
This disorder in inherited in an
autosomal recessive fashion.
Molecular biology
Aminoacylase 1 (ACY1: EC 3.5.14) is a
zinc
Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
binding
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
which hydrolyzes
N-acetyl amino acids into the free
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
and
acetic acid. Of the N-acetyl amino hydrolyzing enzymes, aminoacylase 1 is the most common.
The ACY1 gene is located on the short arm of
chromosome 3
Chromosome 3 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 3 spans almost 200 million base pairs (the building material of DNA) and represents about 6.5 percent of the total DNA in ...
(3p21.2).
Diagnosis
There is a specific pattern of N-acetyl
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
excretion in the urine. The diagnosis can be confirmed by sequencing of the
aminoacylase 1 gene.
Treatment
History
This disorder was first reported in 2005.
[Van Coster RN, Gerlo EA, Giardina TG, Engelke UF, Smet JE, De Praeter CM, Meersschaut VA, De Meirleir LJ, Seneca SH, Devreese B, Leroy JG, Herga S, Perrier JP, Wevers RA, Lissens W (2005) Aminoacylase I deficiency: a novel inborn error of metabolism. Biochem Biophys Res Commun 338(3):1322-1326]
References
External links
{{Amino acid metabolic pathology
Amino acid metabolism disorders
Autosomal recessive disorders