What are ATP7A-related Disorders?
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. The symptoms associated with each condition result from defective copper metabolism throughout the body which causes organ damage.
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, and sagging in the face.
Occipital Horn Syndrome (OHS)
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.
Distal Motor Neuropathy
In rare cases, ATP7A mutations can lead to a variable condition 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).
Females with an ATP7A mutation are usually asymptomatic, although about half express atypical hair findings.
How common are ATP7A-related Disorders?
ATP7A-related disorders are rare. Studies indicate that 1 in 300,000 babies in European populations have Menkes syndrome. The condition is less common in Japan with 1 in 360,000 individuals affected with the condition. Menkes syndrome may be more common in Australia, where some studies estimated that 1 in 50,000 to 1 in 100,000 were affected. The global incidence of occipital horn syndrome and distal motor neuropathy is unknown.
How are ATP7A-related Disorders treated?
These conditions are treated with copper supplementation, which must be given by injection. Early supplementation (within the first few weeks of life) may improve outcomes and increases life expectancy for some children with Menkes syndrome, though less is known about the effects for the other presentations.
In individuals where symptoms have already developed, treatment is symptomatic. For example, a feeding tube may be given to ensure proper nutrition. Early intervention may assist with developmental issues, and physical/occupational therapy and orthopedic aids may improve symptoms due to connective tissue problems.
What is the prognosis for a person with an ATP7A-related Disorder?
Without treatment, children with Menkes syndrome do not typically survive more than three years. Early treatment of Menkes syndrome with copper supplementation can improve outcomes and increase life expectancy. Individuals with OHS live into at least mid-adulthood. Little is known about the success of copper supplementation in OHS. Life expectancy is thought to be unaffected by distal motor neuropathy, but only a few cases of this presentation have been reported and long-term outcomes are unknown.