Long-term outcome of CblC deficiency complicated with pulmonary hypertension

OBJECTIVE: Pulmonary Hypertension (PH) in patients with cblC deficiency is one of the rare but lethal complications. This study aimed to described its characteristics and long-term outcome. METHODS: A total of 26 patients with cblC deficiency complicated by PH were enrolled. Clinical and laboratory data were reviewed in detail. RESULTS: Sixteen patients presented with PH manifestations as the initial symptom while ten patients developed PH after the involvement of other systems. The median onset age of PH was 3.25 years (ranging from 1 month to 13.4 years). Sixteen cases had other cardiovascular damage, including right cardiac enlargement, atrial septal defects, ventricular septal defects, left ventricular hypertrophy, pericardial effusion, pulmonary artery fistula and mild pulmonary artery stenosis. Intramuscular hydroxylcobalamin was given to all patients, together with L-carnitine, betaine and folinic acid after diagnosis. And PH targeted drags were given to 12 cases. As a result, propionylcarnitine, propionylcarnitine/acetylcarnitine ratio, methylmalonic acid, methylcitric acid and homocysteine levels decreased while methionine levels increased remarkably after treatment(p<0.05). The c.80 A> G variant was the most frequent allele in this cohort. Pulmonary artery systolic pressure was within the normal range in all patients, except that one case still had PH and two cases died. Multi-system involvement was improved overall. CONCLUSION: cblC deficiency should be considered in patients with PH. Multi-system evaluation, especially echocardiography is recommended to be performed regularly at each patient visit. The c.80 A > G variant might be a hot-spot mutation of cblC deficiency complicated with PH. Most patients show optimistic prognosis, while neurological damage is usually difficult to reverse.