Onset occurs in the neonatal period. Most patients are born at term with appropriate birth measurements. Cephalohematomas and spontaneous fractures are occasionally observed at birth. In the early neonatal period, patients may present with prolonged jaundice, hypothermia, hypoglycemia and feeding difficulties. Pectus excavatum and umbilical and inguinal hernias have also been reported. The first sign may be unusual sparse and dull scalp hair at the age of 1-2 months. The characteristic abnormal hair is hypopigmented or depigmented and resembles and feels like steel wool. It is dull and friable, especially in the areas of the scalp subjected to friction. Additional symptoms are failure to thrive, poor eating, vomiting, and diarrhea. An odd appearance, with pale skin, frontal or occipital bossing, micrognathia and pudgy cheeks may be observed. Patients develop gradual motor dysfunction and seizures. Muscular tone is often decreased in early life, but is later replaced by spasticity and weakness of the extremities. The clinical course is usually severe. Variable forms exist with occipital horn syndrome (OHS) being the mildest recognized form. Delayed dental eruption can be observed.
The disease is caused by mutations in the ATP7A gene (Xq21.1) encoding a copper-transport protein, Cu2+-transporting ATPase-alpha polypeptide. To date, about 200 different mutations in this gene have been reported. There is no obvious correlation between the mutations and the clinical course.
