An Overview and Update ofATP7AMutations Leading to Menkes Disease and Occipital Horn Syndrome

Abstract

Menkes disease (MD) is a lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar "kinky" hair, are the main manifestations. MD is inherited as an X-linked recessive trait, and as expected the vast majority of patients are males. MD occurs because of mutations in the ATP7A gene and the vast majority of ATP7A mutations are intragenic mutations or partial gene deletions. ATP7A is an energy-dependent transmembrane protein, which is involved in the delivery of copper to the secreted copper enzymes and in the export of surplus copper from cells. Severely affected MD patients die usually before the third year of life. A cure for the disease does not exist, but very early copper-histidine treatment may correct some of the neurological symptoms. This study reviews 274 published and 18 novel disease causing mutations identified in 370 unrelated MD patients, nonpathogenic variants of ATP7A, functional studies of the ATP7A mutations, and animal models of MD.

Contribution of metals to brain MR signal intensity: review articles

“…Copper is obtained orally from the daily diet and is excreted via the biliary system. Copper metabolic abnormalities include Wilson's disease, which is a condition associated with excessive copper accumulation, and Menkes disease, which is a condition related to copper deficiency [87][88][89][90]. Wilson's disease is caused by a mutation in the gene for ATP7B, which binds copper to ceruloplasmin and facilitates the excretion of the copper-ceruloplasmin complex in the bile; the mutation leads to the gradual accumulation of copper in the body [89][90][91].…”

Occipital Horn Syndrome Case Report: Multidisciplinary Approach of a Rare Entity

“…However, genetics has nowadays the main role in this diagnostic process, with the identification of the ATP7A gene mutations enabling the definitive diagnosis [3].…”

“…The mutated gene is ATP7A, encoding a coppertransporting ATPase, localized in the trans-Golgi membrane of the cell, and results in abnormal metabolism and distribution of copper [2][3][4]. It represents a milder form of Menkes disease, characterized by low seric concentrations of normal ATPase and less aggressive phenotype [5].…”

Abnormal Copper Homeostasis: Mechanisms and Roles in Neurodegeneration

“…Menkes' disease (MD) is an X-linked disease due to a mutation of the ATP7A gene. The large majority of patients are males [49]. Most ATP7A mutations are intragenic mutations or partial gene deletions [49].…”

“…The large majority of patients are males [49]. Most ATP7A mutations are intragenic mutations or partial gene deletions [49]. Female carriers are mosaics of wild-type and mutant cells due to the random X inactivation [50].…”