ATP7A-related disorders are a spectrum of diseases that result from improper regulation of copper in the body.
They generally occur in males, as ATP7A, the gene associated with the disorders, is on the X-chromosome. Females are usually asymptomatic. Disease-causing mutations in the ATP7A gene may cause one of three different conditions:
Menkes syndrome, the most typical presentation of this condition, is associated with low or absent serum copper levels. Boys with Menkes syndrome usually start to show symptoms at a few months of age, and symptoms include delayed development or loss of milestones due to progressive neurodegeneration, low muscle tone, poor growth, seizures, and an out-pouching of the bladder. Changes in appearance may be noticeable around symptom onset, including hair with a specific coarse texture, twisting shape and lighter color.
Occipital horn syndrome (OHS) is a milder copper transport disorder, with boys not displaying symptoms until they are several years old. Symptoms in OHS are related to the connective tissues, and typically include loose skin, unstable joints, differences in hair, and calcium deposits of a specific region of the skull that give the condition its name.
In rare cases, ATP7A mutations can lead to a variable condition called distal motor neuropathy that causes weakness in the hands and feet, foot drop (front of foot drops and affects walking), and some absent reflexes. It has been reported in early childhood to late adulthood, but most individuals develop symptoms in adulthood (20s-30s).
This group of conditions is caused by pathogenic (disease-causing) variants in the ATP7A gene and exhibits X-linked recessive inheritance. This means that female carriers will have a 50% chance of having an affected son and a 50% of having daughters who are carriers as well.
Female carriers may be at risk for atypical hair findings.
Other names for this condition are cutis laxa, steely hair syndrome, and X-linked copper deficiency.