Here, we present a unique case of PAH associated with a novel heterozygous mutation in FLNA and a known heterozygous mutation in MMACHC. We observed that PAH-targeted therapies and pulmonary artery denervation (PADN) treatment were well tolerated by our patient and did not lead to heart failure during a 2-year follow-up period. Here, MMACHC is linked to pulmonary arterial hypertension.