Primary pulmonary hypertension after amfepramone (diethylpropion) with BMPR2 mutation

Primary pulmonary hypertension (PPH) is characterised by sustained elevations of pulmonary arterial pressure without a demonstrable cause, leading to right ventricular failure and death. Hereditary mutations in the bone morphogenetic protein receptor type II (BMPR2) gene result in familial PPH transmitted as an autosomal dominant trait, albeit with low penetrance. The causes in cases without a BMPR2 mutation are unknown, but a syndrome of pulmonary arterial hypertension (PAH) similar to hereditary PPH is associated with systemic connective tissue disease, congenital heart disease, portal hypertension, and human immunodeficiency virus infection, or with the use of appetite-suppressant drugs. The authors identified a BMPR2 gene mutation in a 27-yr-old female who developed PAH after a short course of the appetite-suppressant drug amfepramone (diethylpropion). This allowed molecular genetic counselling and prevention of potentially harmful drug exposure in the patient's son treated for attention deficit disorder with methylphenidate, an amphetamine-related drug. No BMPR2 mutation was found in four additional, unrelated patients with appetite suppressant-related PPH. The findings provide strong evidence that amfepramone can trigger primary pulmonary hypertension in a bone morphogenetic protein receptor type II gene mutation carrier, and indicate that other genes are probably implicated in genetic susceptibility to appetite suppressants.