Menkes disease complicated by concurrent ACY1 deficiency: A case report

Introduction: Menkes disease is an X-linked recessive condition caused by mutations in the ATP7A gene, which leads to severe copper deficiency. Aminoacylase-1 deficiency is a rare inborn error of metabolism caused by homozygous or compound heterozygous variant in the ACY1 gene, characterized by increased urinary excretion of specific N-acetyl amino acids.Case presentation: We report an infant with neurological findings such as seizures, neurodevelopmental delay and hypotonia. Metabolic screening showed low serum copper and ceruloplasmin, and increased urinary excretion of several N-acetylated amino acids. Whole-exome sequencing analysis (WES) revealed the novel de novo variant c.3642_3649dup (p.Ala1217Aspfs*2) in the ATP7A gene, leading to a diagnosis of Menkes disease, and the simultaneous presence of the homozygous ACY1 variant c.1057C > T (p.Arg353Cys) causative of Aminoacylase-1 deficiency.Conclusion: Our patient had two rare conditions with different treatment courses but overlapping clinical features. The identified novel ATP7A mutation associated with Menkes disease expands the ATP7A gene spectrum.

Automated summary

In this study, we report an infant with both Menkes disease and Aminoacylase-1 deficiency, characterized by neurological symptoms such as seizures, neurodevelopmental delay, and hypotonia. Genetic sequencing revealed mutations in the ATP7A and ACY1 genes, contributing to the development of these two rare conditions. This research expands the mutation spectrum of the ATP7A gene.