Yan Wu, Yuan-Rui Deng, Xiao-Pei Cui, Sheng-Song Zhu, Jiang Shan Tan, Song Hu, Lu Hua
Fuwai Hospital, Fuwai Shenzhen Hospital and Peking Union Medical College. Qilu Hospital of Shandong University.
China
Journal of Heart and Lung Transplantation
J Heart Lung Transplant 2026;
DOI: 10.1016/j.healun.2026.07.021
Abstract
Background: Methylmalonic acidemia (MMA)-induced pulmonary hypertension (PH) is a rare but treatable cause of pediatric PH, often misdiagnosed as idiopathic pulmonary arterial hypertension (IPAH).
Methods: We conducted a 10-year, multicenter retrospective study of children with clinically unexplained PH. Thirteen patients with MMA-PH were compared to 113 with idiopathic or hereditary PAH (IPAH/HPAH) regarding clinical features, hemodynamics, and outcomes.
Results: MMA-PH accounted for 2.7% of pediatric PH cases. Patients presented younger (7±4 vs. 11±5 years, p=0.008) and exhibited higher rates of growth failure (84.6% vs. 15.9%, p<0.001), anorexia/malnutrition (76.9% vs. 14.2%, p<0.001), recurrent pneumonia (46.2% vs. 13.3%, p=0.003), microscopic hematuria (84.6% vs. 1.8%, p<0.001), and proteinuria (31% vs. 4.4%, p=0.007) than IPAH/HPAH. All had the combined MMA subtype with markedly elevated homocysteine (median 87 µmol/L vs. 18 µmol/L, p<0.001). With metabolic therapy (hydroxocobalamin, betaine, etc.) and short-term pulmonary vasodilators, all achieved complete clinical and hemodynamic remission within one year. Median follow-up was 7.0 years; no relapse occurred.
Conclusions: Elevated total homocysteine and multisystem involvement should prompt metabolic screening in children with unexplained PH. Early diagnosis and metabolite-targeted treatment can lead to sustained, nearly-curative outcomes, distinguishing MMA-PH from IPAH/HPAH. Routine homocysteine testing is recommended in the diagnostic workup of pediatric PH.
Category
Class I. Heritable Pulmonary Hypertension
Symptoms and Findings Associated with Pulmonary Vascular Disease
Medical Therapy. Efficacy or Lack of Efficacy
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
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