Recent Advances in Understanding Menkes Disease: From Copper Metabolism to Emerging Therapies

Abstract

Menkes disease is a rare X-linked disorder of copper metabolism caused by mutations in the ATP7A gene, resulting in impaired copper transport and deficiency in essential tissues, particularly the brain. Copper is a vital cofactor for several enzymes involved in energy production, neurotransmitter synthesis, and connective tissue formation. Disruption of copper homeostasis leads to progressive neurodegeneration and systemic abnormalities. This review discusses the underlying mechanisms of copper metabolism, the genetic basis of ATP7A dysfunction, and the resulting pathophysiological changes. It also highlights the clinical presentation, including characteristic hair abnormalities, neurological deterioration, and connective tissue defects, along with current diagnostic approaches. Therapeutic strategies such as copper histidine supplementation are evaluated, with emphasis on the importance of early intervention. In addition, emerging treatment approaches, including gene therapy, are briefly addressed as potential future options for disease management. These advancements may improve survival, reduce neurological impairment, and offer hope for better long-term clinical outcomes in affected individuals.