Menkes disease

Menkes disease, also known as Menkes kinky hair disease or copper transport disease, is a severe X-linked recessive disorder of copper metabolism caused by pathogenic variants in the ATP7A gene. This gene encodes a copper-transporting ATPase that is essential for the proper distribution of copper throughout the body. When this transporter is deficient, copper accumulates in certain tissues (such as the intestinal lining and kidneys) while the brain, liver, and other vital organs become severely copper-depleted. Since copper is a critical cofactor for numerous enzymes, this deficiency leads to widespread dysfunction affecting the nervous system, connective tissue, vasculature, and skeletal system. Classic Menkes disease typically presents in early infancy, often between 2 and 3 months of age, with progressive neurodegeneration, seizures, failure to thrive, and hypotonia. A hallmark feature is the characteristic sparse, coarse, and kinky or steely hair due to defective keratin cross-linking. Additional features include hypothermia, connective tissue abnormalities (such as lax skin, bladder diverticula, and vascular tortuosity), skeletal changes including wormian bones and osteoporosis, and subdural hematomas. Affected infants often appear normal at birth but rapidly deteriorate, with most children dying in early childhood, typically before the age of 3 years without treatment. The primary treatment for Menkes disease is early subcutaneous administration of copper histidine (copper-histidinate), which can improve outcomes if initiated within the neonatal period before irreversible neurological damage occurs. Newborn screening approaches measuring low serum copper and ceruloplasmin levels, along with elevated plasma catechol ratios, are being investigated to enable earlier diagnosis. Despite treatment, many patients with classic Menkes disease still experience significant neurological impairment. Milder allelic variants of ATP7A-related copper transport disorders exist, including occipital horn syndrome, which has a less severe phenotype with predominantly connective tissue manifestations. Supportive care including seizure management, nutritional support, and physical therapy remains an important component of management.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Menkes disease