Aminoacylase 1 deficiency

Aminoacylase 1 deficiency (also known as ACY1 deficiency or N-acylaminoacid hydrolase deficiency) is a rare inborn error of metabolism 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 elevated amounts in the urine, which serves as the primary biochemical marker for diagnosis. The clinical significance of aminoacylase 1 deficiency remains somewhat uncertain, as the phenotype is highly variable. Some affected individuals present with neurological features including intellectual disability, seizures, delayed psychomotor development, and autistic features, while others identified through metabolic screening appear to be clinically asymptomatic. Additional reported symptoms in some patients include muscular hypotonia, hearing impairment, and growth delay. The nervous system appears to be the primary body system affected in symptomatic individuals, though the exact pathophysiological mechanism linking enzyme deficiency to neurological dysfunction is not fully understood. There is currently no specific or curative treatment for aminoacylase 1 deficiency. Management is supportive and symptomatic, focusing on addressing developmental delays through early intervention programs, physical therapy, occupational therapy, speech therapy, and seizure management with anticonvulsant medications when needed. Genetic counseling is recommended for affected families. The condition was first described in 2005, and the number of reported cases remains limited, making it difficult to fully delineate the natural history and clinical spectrum of the disorder.

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