An overview and update of ATP7A mutations leading to Menkes disease and occipital horn syndrome

Hum Mutat. 2013 Mar;34(3):417-29. doi: 10.1002/humu.22266.


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.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Alleles
  • Animals
  • Cation Transport Proteins / genetics*
  • Child, Preschool
  • Chromosome Aberrations
  • Copper / metabolism
  • Copper-Transporting ATPases
  • Cutis Laxa / diagnosis*
  • Cutis Laxa / genetics*
  • Disease Models, Animal
  • Ehlers-Danlos Syndrome / diagnosis*
  • Ehlers-Danlos Syndrome / genetics*
  • Female
  • Gene Deletion*
  • Genetic Association Studies
  • Humans
  • Infant
  • Male
  • Menkes Kinky Hair Syndrome / diagnosis*
  • Menkes Kinky Hair Syndrome / genetics*
  • Mice
  • Phenotype


  • Cation Transport Proteins
  • Copper
  • Adenosine Triphosphatases
  • ATP7A protein, human
  • Copper-Transporting ATPases

Supplementary concepts

  • Occipital horn syndrome