Abstract
Menkes' disease is a rare X-linked neurodegenerative disorder due to an ATPA7 mutation.
This mutation results in a defective copper transport into the lumen of the trans-Golgi
network (TGN) of all tissues, except the liver. As the liver remains effective in
transporting copper into the TGN, parenteral copper administration is successful in
normalizing copper and ceruloplasmin levels. In addition, such treatment improves
function of cuproenzymes in the nucleus, cytosol, and mitochondria. However, ATPA7
mutation results in a deficient dopamine β-hydroxylase, a cuproenzyme needed to convert
dopamine to norepinephrine (NE). Here, we present the novel use of the synthetic amino
acid analog, droxidopa, a prodrug to NE in the management of Menkes' disease. In our
6-year-old Menkes' disease patient treated with daily parenteral copper infusion,
we studied clinical features and urine catecholamines levels at baseline and after
initiating droxidopa therapy. NE deficiency at baseline was associated with inattention,
hypothermia, and dysautonomia. After correction of NE deficiency, the child's symptoms
improved. Epinephrine levels remained low. In Menkes' disease, NE deficiency persists
after normalization of copper and ceruloplasmin levels. Droxidopa therapy is successful
in correcting NE levels and improving quality of life. Further studies are needed.
Keywords
dopamine β-hydroxylase - Menkes - ATP7A - amino acid analog
