What are the symptoms of Menkes disease?

Patients with Menkes disease may experience any of the following signs and symptoms1,2

Newborn illustration with Menkes disease and signs and symptoms caused by copper transport deficiency

Urological symptoms

  • Bladder diverticula
  • Hernia
  • Urinary tract infection

GI symptoms

  • Failure to thrive
  • Gastric polyps
  • Acid reflux

Respiratory infections

  • Respiratory failure

Vascular disease

  • Congenital heart disease
  • Arterial aneurysms
  • Cerebral hemorrhage

Neurological symptoms

  • Seizures
  • Hypotonia
  • Developmental delays
  • Ataxia

Kinky and/or steely, dry, brittle hair

Connective tissue abnormalities

  • Facial dysmorphism
  • Loose skin
  • Pectus exacavatum
  • Pectus carinatum
  • Wormian bones in skull


  • Osteoporosis
  • Rib fractures

Early signs and symptoms may be present in neonates with Menkes disease1

Pregnancy and labor are typically normal for infants born with Menkes disease, although early birth is common. Most infants present with no overt signs of disease at birth but develop symptoms within 6-8 weeks of age. However, some early non-specific features may be present, including1,3:

  • Hypothermia or temperature instability
  • Cephalohematomas
  • Persistent hyperbilirubinemia
  • Hypoglycemia
  • Feeding difficulties
  • Dull and expressionless facial features
  • Facial dysmorphism (such as frontal or occipital prominence, pudgy cheeks with a broad nasal bridge, or micrognathia)
Woman holding baby with Menkes disease

Early signs and symptoms suggestive of Menkes disease should lead to clinical suspicion, additional testing, and diagnosis.1

Depending on the residual ATP7A activity preserved, different mutations can give rise to a spectrum of disease severity1,4

ATP7A residual function 60-70% function <30% function <15% function
Symptoms Mild Moderate Severe
Age of onset Adulthood Childhood <12 months
  • More severe symptoms associated with Menkes disease, such as seizures or intellectual disabilities, may not be present in patients with milder ATP7A mutations1
  • ATP7A variants with higher remaining residual function correlate with later age of onset and longer life expectancy1,4

Patients with untreated severe Menkes disease usually have a life span between 6 months and 3 years of age1

  • References:
    1. Ojha R, Prasad AN. Menkes disease: what a multidisciplinary approach can do. J Multidiscip Healthc. 2016;9:371-385.
    2. Hicks JD, Donsante A, Pierson TM, Gillespie MJ, Chou DE, Kaler SG. Increased frequency of congenital heart defects in Menkes disease. Clin Dysmorphol. 2012;21(2):59-63.
    3. Kaler SG. ATP7A-related copper transport diseases—emerging concepts and future trends. Nat Rev Neurol. 2011;7(1):15-29.
    4. Horn N, Wittung-Stafshede P. ATP7A-regulated enzyme metalation and trafficking in the Menkes disease puzzle. Biomedicines. 2021;9(4):391.