Aminoacylase deficiency

Aminoacylase deficiency (also known as aminoacylase 1 deficiency or ACY1 deficiency) is an ultra-rare inherited metabolic disorder caused by mutations in the ACY1 gene, which encodes the enzyme aminoacylase 1. This enzyme is responsible for the hydrolysis of N-acetylated amino acids, a final step in intracellular protein degradation. When the enzyme is deficient, N-acetylated amino acids accumulate and are excreted in excess in the urine, which serves as a key biochemical marker for diagnosis. The clinical presentation of aminoacylase 1 deficiency is highly variable. Some affected individuals present in infancy or early childhood with neurological features including intellectual disability, developmental delay, seizures, and motor impairment. Other reported features include hearing loss and autistic features. However, some individuals identified through metabolic screening have been reported to be asymptomatic, raising questions about the full clinical significance of the enzymatic deficiency. The nervous system appears to be the primary organ system affected in symptomatic patients. There is currently no specific curative treatment for aminoacylase 1 deficiency. Management is supportive and symptomatic, focusing on developmental therapies, seizure management when applicable, and monitoring of neurological function. Genetic counseling is recommended for affected families. Due to the rarity of the condition, understanding of the natural history and genotype-phenotype correlations remains limited, and further research is needed to clarify the spectrum of disease severity.

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