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Primary pulmonary hypertension after amfepramone (diethylpropion) with BMPR2 mutation
M J Abramowicz1, P Van Haecke, M Demedts
1Service de Génétique Médicale, Hôpital Erasme-Université Libre de Bruxelles, Brussels, Belgium. marcabra@ulb.ac.be
Abstract:
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.
Insights
A bone morphogenetic protein receptor type II (BMPR2) gene mutation carrier developed pulmonary arterial hypertension (PAH) after using the appetite suppressant amfepramone. This highlights the drug
Area of Science:
- Genetics
- Cardiology
- Pharmacology
Background:
- Primary pulmonary hypertension (PPH) involves elevated pulmonary arterial pressure, leading to right ventricular failure.
- Hereditary PPH is linked to bone morphogenetic protein receptor type II (BMPR2) gene mutations, inherited in an autosomal dominant pattern with incomplete penetrance.
- Pulmonary arterial hypertension (PAH) can also be associated with connective tissue diseases, congenital heart disease, portal hypertension, HIV, or appetite-suppressant drugs.
Observation:
- A 27-year-old female with a BMPR2 gene mutation developed PAH after a brief course of the appetite suppressant amfepramone (diethylpropion).
- Genetic counseling was provided, leading to the prevention of potentially harmful drug exposure for her son, who was treated for attention deficit disorder with methylphenidate.
- No BMPR2 mutation was identified in four other unrelated patients with PPH linked to appetite suppressant use.
Findings:
- The study provides strong evidence that amfepramone can trigger primary pulmonary hypertension in individuals with a BMPR2 gene mutation.
- The findings suggest that other genetic factors likely contribute to susceptibility to appetite suppressant-induced pulmonary hypertension.
Implications:
- This research underscores the critical importance of considering genetic predispositions when evaluating patients with drug-induced pulmonary arterial hypertension.
- Identifying BMPR2 mutations can inform personalized medicine approaches, including pharmacogenetic counseling and the avoidance of specific drug classes.
- Further research into the genetic underpinnings of appetite suppressant-related PAH is warranted to identify additional susceptibility genes.
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