Abstract:
Menkes disease is a rare, X-linked recessive disorder caused by mutations in the ATP7A(ATPase Copper Transporting Alpha) gene, which encodes a copper-transporting ATPase essential for maintaining copper homeostasis. Copper is a vital trace element required for critical physiological processes, including energy production, connective tissue formation, and neurotransmitter synthesis. Mutations in ATP7A disrupt copper transport, leading to systemic copper deficiency and dysfunction of copper-dependent enzymes. Clinically, Menkes disease is characterized by progressive neurodegeneration, brittle and kinky hair (pili torti), developmental delays, seizures, and skeletal abnormalities. Without timely intervention, the disease often results in severe disability or death by early childhood. Current treatment options, such as parenteral copper histidinate, provide limited efficacy, highlighting the urgent need for advanced therapeutic approaches. Despite its critical role, ATP7A remains incompletely characterized, with its full structure not yet resolved. Intriguingly, ATP7A shares high structural and functional similarity with ATP7B, another copper-transporting ATPase associated with Wilson disease. However, mutations in ATP7A result in systemic copper deficiency, whereas ATP7B mutations lead to copper accumulation, underscoring the divergent pathophysiological outcomes despite their similarities.
