Primary pulmonary hypertension after amfepramone (diethylpropion) with BMPR2 mutation

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.