Aminoacylase 1 deficiency

Jorn Oliver Sass Dr rer nat (Dr. Sass of Bonn-Rhein Sieg University of Applied Sciences has no relevant financial relationships to disclose.)
Barry Wolf MD PhD, editor. (Dr. Wolf of Lurie Children's Hospital of Chicago has no relevant financial relationships to disclose.)
Originally released May 17, 2010; last updated December 13, 2019; expires December 13, 2022

This article includes discussion of aminoacylase 1 deficiency, acylase 1 deficiency, ACY1 deficiency, and N-acyl-L-amino acid amidohydrolase. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Aminoacylase 1 deficiency is an inborn error of amino acid metabolism that is probably underdiagnosed because of lack of awareness. In this article, the author provides an overview of the current knowledge of this metabolic disorder.

Key points


• Aminoacylase 1 deficiency is an organic aciduria with enhanced excretion of N-acylated amino acids.


• Aminoacylase 1 deficiency is an inborn error of metabolism that follows an autosomal recessive trait of inheritance.


• Most individuals with aminoacylase 1 deficiency exhibit neurologic symptoms.


• Due to the young age of most ACY1-deficient individuals, the clinical course and natural history of the disorder cannot be predicted.

Historical note and terminology

In 1881, Schmiedeberg discovered intracellular enzymatic activity catalyzing the hydrolysis of N-benzoylglycine (hippuric acid). This enzymatic activity, named “Histozym” (tissue enzyme) by Schmiedeberg, also catalyzes the hydrolysis of various other acylated amino acids and was, therefore, later named aminoacylase 1 (ACY1; EC (Smorodinzew 1922). Birnbaum and colleagues reported aliphatic amino acids with a short-chain acyl moiety, especially N-acetyl-methionine, as preferred substrates of ACY1 (Birnbaum et al 1952). However, this enzyme not only has a role in hydrolysis but also can catalyze the synthesis of N-acetylated amino acids (Lindner et al 2000). The aminoacylase 1 enzyme is encoded by the ACY1 gene on chromosome 3p21 (Naylor et al 1979; Naylor et al 1982; Miller et al 1990). Notably, N-acetylaspartate is not a substrate of ACY1, but of aminoacylase 2 (ACY2, aspartoacylase; EC, encoded by the ASPA gene. Mutations in the ASPA gene resulting in ACY2 deficiency are known to cause Canavan disease (MIM 271900) (Kaul et al 1993; Baslow and Resnik 1997), a neurodegenerative disease that usually results in death in early childhood (Canavan 1931; Moffett 2007). In contrast to individuals with Canavan disease, those with aminoacylase 1 deficiency have only been identified recently. They have all presented with a characteristic pattern of urinary N-acylated amino acids, which is usually detectable on routine urinary organic acid analysis (Sass and Sewell 2001). However, it is likely that other individuals with the deficiency are not readily identified.

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