Menkes disease (MD) is caused by an X-linked inherited genetic mutation of the Cu-ATPase ATP7A. Since, it is an X-linked disorder, predominantly affects to the male population. It is the fatal disease for the children which can cause lethality within first 3 years of life. The hallmarks of MD are unusual sparse kinky hair on the scalp of the infants and decreased muscle tone and delayed milestones. The milder form of this mutation is known as occipital horn syndrome (OHS) also known as Ehlers-Danlos syndrome type IX which presented with the wedge-shaped protruded calcification at the area of occipital bone. OHS is the mostly due to the leaky splice junctions as the result of exon skipping mutations with some residual functioning of ATP7A transporter. So, Cu transport is not completely ablated, and Cu can still be exported at some extent. ATP7A transporter is ubiquitously found in the body and localized in the trans-Golgi network within the cellular compartment for metalation of the secreted cuproenzymes, such as lysyl oxidase, tyrosinase and extracellular SOD. Mutations of ATP7A impairs the absorption of dietary Cu, preventing it from crossing the intestinal epithelial barrier through the trans Golgi secretory pathway, and therefore the ion is not properly distributed systemically. There are over 200 known mutations of ATP7A, of which 25% are associated to the deletion of exons, ranging from a single exon, to almost the entire gene with the exception of the first 2 exons. Additional mutations throughout the Atp7a gene are nonsense, missense, splice-site, and point mutations which result in different phenotypes and severity of the disease.
