The Novel Use of a Synthetic Amino Acid Analog in the Management of Menkes' Disease

Abstract

AbstractMenkes' 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.