Boglarka Bansagi, MD, David Lewis-Smith, MRCP, Endre Pal, MD, PhD, Jennifer Duff, PhD, Helen Griffin, PhD, Angela Pyle, PhD, Juliane S. Müller, PhD, Gabor Rudas, MD, PhD, Zsuzsanna Aranyi, MD, PhD, Hanns Lochmüller, MD, Patrick F. Chinnery, FRCP, FMedSci and Rita Horvath, MD, PhD
Menkes disease is an X-linked multisystem disorder with epilepsy, kinky hair, and neurodegeneration caused by mutations in the copper transporter ATP7A. Other ATP7A mutations have been linked to juvenile occipital horn syndrome and adult-onset hereditary motor neuropathy. About 5%–10% of the patients present with “atypical Menkes disease” characterized by longer survival, cerebellar ataxia, and developmental delay. The intracellular copper transport is regulated by 2 P type ATPase copper transporters ATP7A and ATP7B. These proteins are expressed in the trans-Golgi network that guides copper to intracellular compartments, and in copper excess, it relocates copper to the plasma membrane to pump it out from the cells. ATP7B mutations cause Wilson disease with dystonia, ataxia, tremor, and abnormal copper accumulation in the brain, liver, and other organs.