Cobalamin C deficiency presenting with diffuse alveolar hemorrhage and pulmonary microangiopathy

摘要

Abstract Objective Combined methylmalonic acidemia and homocysteinemia is a genetically heterogeneous disorder of cobalamin (cbl; vitamin B12) metabolism, which consists of five subtypes including cblC, cblD, cblF, cblJ, and cblX deficiencies. The purpose of this study is to summarize new clinical features mainly diffuse alveolar hemorrhage (DAH) in cblC deficiency. Methods We made a retrospective analysis of four pediatric patients diagnosed with DAH and pulmonary microangiopathy due to cblC deficiency between January 2017 and December 2018 in Beijing Children's Hospital. Results This study describes four patients with their ages ranging from 4 years 2 months to 7 years 6 months with cblC deficiency who developed late‐onset diffuse lung disease (DLD). Of these, the first three patients presented predominantly with DAH, and the last patient with pulmonary microangiopathy confirmed by thoracoscopic lung biopsy. All patients were accompanied by pulmonary arterial hypertension (PAH), two accompanied by respiratory failure, and two accompanied by moderate megaloblastic anemia. Diffuse ground‐glass opacification and poorly defined ground‐glass centrilobular nodules were seen on high‐resolution computed tomography in one patient and three patients, respectively. All patients were suspected of having idiopathic pulmonary hemosiderosis or interstitial lung disease at other hospitals. All of them received treatment with corticosteroid before admission, but the symptoms did not improve. Moreover, all patients carried compound heterozygous mutations (c.80AG, c.609GA) in MMACHC and improved significantly after being treated for cblC deficiency and PAH. Conclusions CblC deficiency should be considered in the differential diagnosis of DAH especially with PAH, and pulmonary microangiopathy be the main reason of DLD in these patients.