General description

Menkes disease is an X-linked recessive neurodegenerative disorder caused by mutations in the ATP7A gene, which affects copper transport. This leads to copper deficiency and reduced activity of copper-dependent enzymes, resulting in abnormalities in connective tissue, blood vessels, and hair. The disease typically manifests in infancy with symptoms such as fine, silvery, and brittle hair (kinky hair) and loose skin due to connective tissue disturbances.

Infants with Menkes disease experience progressive neurologic deterioration, often starting with seizures in the first few days or months of life, followed by progressive hypotonia and developmental delay within the first year. Other common features include pectus excavatum, failure to thrive or gain weight, and urinary bladder diverticula. Early treatment with parenteral copper histidine may halt the progressive neurodegeneration.

The ATP7A gene, located on Xq13.3, encodes a copper-transporting ATPase, and mutations in this gene disrupt copper transport into cells, causing copper deficiency and mitochondrial dysfunction due to the lack of copper-containing mitochondrial enzymes.