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  • Updated 12.28.2023
  • Released 05.17.2010
  • Expires For CME 12.28.2026

Aminoacylase 1 deficiency



Aminoacylase 1 deficiency is an inborn error of amino acid metabolism that is probably underdiagnosed because of a 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 (29). Birnbaum and colleagues reported aliphatic amino acids with a short-chain acyl moiety, especially N-acetyl-methionine, as preferred substrates of ACY1 (04). However, this enzyme not only has a role in hydrolysis but also can catalyze the synthesis of N-acetylated amino acids (13). The aminoacylase 1 enzyme is encoded by the ACY1 gene on chromosome 3p21 (21; 20; 16).

Notably, N-acetylaspartate is not a substrate of ACY1, but of aminoacylase 2 (ACY2, aspartoacylase; EC, encoded by the ASPA gene. An aspartoacylase deficiency results in Canavan disease (12). Mutations in the ASPA gene resulting in ACY2 deficiency are known to cause Canavan disease, characterized by isolated elevation of N-acetylaspartic acid in body fluids (MIM 271900) (10; 03); Canavan disease is a neurodegenerative disease that often results in death in early childhood (05; 18). 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. However, it is likely that other individuals with the deficiency are not readily identified.

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