Menkes disease overview

What is Menkes disease

Menkes disease is a disorder characterized by defective copper transport and metabolism1

Menkes disease is an X-linked recessive disorder caused by mutations in the transport ATPase encoded by ATP7A.1,2 Menkes disease is a rare disease, with recent estimates suggesting a prevalence of 1 in 34,810 to as high as 1 in 8,664 live male births.3

Patients with Menkes disease are born with the inability to absorb dietary copper and subsequently have impaired copper transport across the blood-brain barrier.1,2

Menkes disease is also known as1:

  • Menkes syndrome
  • Kinky hair disease
  • Steely hair disease
  • Menkes kinky hair disease
  • Menkes steely hair disease
  • Trichopoliodystrophy

The pathophysiology of impaired absorption and transport in patients with ATP7A mutations1,4

Illustration showing copper transport deficiency caused by ATP7A mutations in Menke disease hCTR1
hCTR1

Adapted from Bandmann et al.

Mutations in ATP7A lead to disruptions in processes essential for normal human physiology2

The biological functions altered by mutations in ATP7A include2:

Molecule representing changes in cellular metabolism caused by ATP7A mutations

Cellular metabolism

Shield representing deficiency in cellular protection caused by ATP7A mutations

Cellular protection

Interlocking circles representing connective tissue formation affected by ATP7A mutations in Menkes syndrome

Connective tissue formation

Paint tube representing pigment formation decreased in Menkes disease patients

Pigment formation

Synapse with neurotransmitters showing abnormal catecholamine synthesis in patients with Menkes kinky hair disease

Catecholamine synthesis

ATP7A mutations impact the transport of copper to a range of organs and systems, which can lead to the dysfunction of copper-dependent enzymes.1,2

Newborn illustration with Menkes disease showing organs and enzymes affected by copper deficiency

Bladder

Stomach/Intestines

Lungs

Heart

Brain

Hair

Connective tissue

Skeleton

Bladder

  • Lysyl oxidase

Stomach/Intestines

  • Ceruloplasmin
  • Hephaestin

Lungs

  • Lysyl oxidase
  • Cytochrome c oxidase

Heart

  • Lysyl oxidase

Brain

  • Cytochrome c oxidase
  • Superoxide dismutase
  • Dopamine ß hydroxylase

Hair

  • Sulfhydryl oxidase
  • Tyrosinase

Connective tissue

  • Lysyl oxidase

Skeleton

  • Lysyl oxidase

Dysregulation of copper-dependent enzymes leads to multisystem signs and symptoms.

  • References:
    1. Ojha R, Prasad AN. Menkes disease: what a multidisciplinary approach can do. J Multidiscip Healthc. 2016;9:371-385.
    2. Tümer Z, Møller LB. Menkes disease. Eur J Hum Genet. 2010;18(5):511-518.
    3. Kaler SG, Ferreira CR, Yam LS. Estimated birth prevalence of Menkes disease and ATP7A-related disorders based on the Genome Aggregation Database (gnomAD). Mol Genet Metab Rep. 2020;24:100602.
    4. Bandmann O, Weiss KH, Kaler SG. Wilson’s disease and other neurological copper disorders. Lancet Neurol. 2015;14(1):103-113.