Pulmonary hypertension associated with methylmalonic acidemia (PH-MMA) is rare but often fatal. We reported 30 cases of pediatric PH-MMA.
We retrospectively and prospectively studied 30 children with PH –MMA. Documentation of clinical, biochemical, and chest HRCT features, and level of pulmonary arterial systolic pressure(PASP) estimated through tricuspid regurgitation by Doppler Echocardiogram was done. MMA Genome was analyzed. Short time and longitudinal response to treatment was followed-up while standard treatment was applied.
There were 24 male and 6 female patients aged 5.8±4.0 years. Gene testing reveals cblC deficiency in all of the 21 cases tested. PH was the leading manifestation of MMA in 20 cases, and in the other 10 patients, PH developed 3-75 months after other system involved, the interval between the two disease onset was 0 to 75 months. The main symptoms of PH-MMA were tachypnea/dyspnea(67.6%), fatigue(53.3%) and cyanosis(43.3%). Hypoxia was a common finding(85%). WHO Functional Class was 3.3±0.8. The estimated PASP was 89.3±23.9mmHg( 47~135mmHg) at PH diagnosis. Plasma BNP level severely elevated to 2176.4±2048.8 pg/ml. Chest HRCT showed a diffuse ground-glass centrilobular nodular opacities with septal line thickening in the lungs in 23 cases, indicating pulmonary veno-occlusive disease(PVOD). Symptoms remarkably resolved and PH reversed in 20 patients after 3-6 months treatment of both MMA and PH, and plasma homocystein level dropped dramatically and BNP returned to normal in all the 20 cases and without recurrence. Totally 8patients died of heart and/or respiratory failure within one week of diagnosis.
PH-MMA is a severe type of PH with high short-term mortality. It may develop in MMA combined type, mainly cblC deficiency boys. Hypoxia and PVOD feature in Chest HRCT is of characteristic. PH-MMA is reversible by timely diagnosis and effective treatment of both MMA and PH.