Menkes disease complicated by concurrent ACY1 deficiency: A case report

Area of Science:

• Genetics
• Metabolic Disorders
• Neurodevelopmental Disorders

Background:

• Menkes disease is an X-linked recessive disorder caused by ATP7A gene mutations, leading to copper deficiency.
• Aminoacylase-1 deficiency is a rare metabolic disorder due to ACY1 gene variants, marked by increased urinary N-acetyl amino acids.
• Both conditions can present with overlapping neurological symptoms, complicating diagnosis.

Observation:

• A patient presented with seizures, neurodevelopmental delay, and hypotonia.
• Metabolic screening revealed low serum copper and ceruloplasmin, alongside elevated urinary N-acetylated amino acids.
• Whole-exome sequencing identified a novel de novo ATP7A variant and a homozygous ACY1 variant.

Findings:

• The patient was diagnosed with both Menkes disease and Aminoacylase-1 deficiency.
• A novel de novo variant (c.3642_3649dup, p.Ala1217Aspfs*2) in the ATP7A gene was identified, confirming Menkes disease.
• A homozygous ACY1 variant (c.1057C>T, p.Arg353Cys) was found, causative of Aminoacylase-1 deficiency.

Implications:

• This case highlights the diagnostic challenge of co-occurring rare genetic disorders with overlapping phenotypes.
• The identification of a novel ATP7A mutation expands the mutational spectrum for Menkes disease.
• Understanding these dual diagnoses is crucial for appropriate management and genetic counseling.