Menkes Disease (ATP7A)
Menkes disease is a pan-ethnic disorder of copper deficiency that is caused by pathogenic variants in the ATP7A gene. It is inherited in an X-linked manner, and therefore males are affected more often and more severely than females. Pathogenic variants in ATP7A result in the inefficient activity of several enzymes that require copper to function. Clinical features include intrauterine growth retardation and small stature; neurologic deterioration leads to seizures, intellectual disability and abnormal tensing of muscles. Bones and joints may be weak and the head may be small. A characteristic feature is the appearance of the hair, which is twisted, steely, and usually grey in color (pili torti). In the common, severe form of the disease, death occurs by about 3 years of age. Some patients with pathogenic ATP7A variants have a milder disorder called occipital horn syndrome, which is characterized by cognitive deficiencies, loose skin, and a bump on the back of the head near the neck. The milder form of ATP7A deficiency results from variants that retain some residual protein function. Therefore, in some cases it may be possible to predict the severity of the disease a patient may experience.
For information about carrier frequency and residual risk, please see the residual risk table.