Metabolic and genetic assessments interpret unexplained aggressive pulmonary hypertension induced by methylmalonic acidemia: A case report

BACKGROUND: Pulmonary hypertension (PH) causes significant morbidity and mortality in diverse childhood diseases. However, limited information has been reported to obtain a good understanding of pediatric PH. Gaps exist between genome sequencing and metabolic assessments and lead to misinterpretations of the complicated symptoms of PH. Here, we report a rare case of a patient who presented with severe PH as the first manifestation without significant cardiovascular malformation and was finally diagnosed with methylmalonic aciduria (MMA) after metabolic and genomic assessments. CASE SUMMARY: An 11-year-old female presented with an aggressive reduction in activity capability and shortness of breath for only 4 mo and suffered from unexplained PH. A series of examinations was performed to evaluate any possible malformations or abnormalities of the cardiovascular system and lungs, but negative results were obtained. The blood tests were normal except for manifestations of microcytic anemia and elevated total homocysteine. Computed tomography and magnetic resonance imaging failed to identify any pulmonary diseases. Cardiac catheterization examination identified a small right coronary artery to pulmonary artery shunt and severe PH. During the follow-up, PH progressed rapidly. Then, genome sequencing and metabolic disorder screening were performed, which confirmed a diagnosis of MMA with MMACHC c.80A > G/c and 609G > A mutations. Vitamin B12, betaine and bosentan were then administered as the main treatments. During the 6-mo follow-up, the pulmonary artery pressure dropped to 45 mmHg, while the right ventricle structure recovered. The patient’s heart function recovered to NYHA class II. Metabolic disorder analysis failed to identify significant abnormalities. CONCLUSION: As emerging types of metabolic dysfunction have been shown to present as the first manifestation of PH, and taking advantage of next generation sequencing technology, genome sequencing and metabolic disorder screening are recommended to have a more superior role when attempting to understand unclear or aggressive PH.