Combined methylmalonic acidemia and homocysteinemia presenting predominantly with late-onset diffuse lung disease: a case series of four patients

Abstract

Combined methylmalonic acidemia (MMA) and homocysteinemia are a group of autosomal recessive disorders caused by inborn errors of cobalamin metabolism, including CblC, D, F, and J, with cblC being the most common subtype. The clinical manifestations of combined MMA and homocysteinemia vary, but typically include neurologic, developmental and hematologic abnormalities.We report 4 children with combined MMA and homocysteinemia who presented predominantly with late-onset diffuse lung diseases (DLD). Of these, 3 accompanied by pulmonary arterial hypertension (PAH), 1 accompanied by hypertension, and 2 accompanied by renal thrombotic microangiopathy (TMA), which was confirmed by renal biopsy. This confirms combined MMA and homocysteinemia should be considered in the differential diagnosis of DLD with or without PAH or renal TMA.

Keywords: Children; Diffuse Lung disease; Homocysteinemia; Homocystinuria; Hypertension arterial pulmonary; Methylmalonic acidemia.

Fig. 1

Lung CT showing the presence in both lungs of 1a diffuse ground-glass opacification predominant in lower region of lung and areas with smooth thickening of interlobular septum (on admission; Patient 1), 1b absence of abnormal pulmonary feature(after 1 month of treatment; Patient 1), 2a interlobular septal thickening and bilateral pleural effusion (1 year before admission; Patient 2), 2b diffuse poorly defined centrilobular nodules(5 days after treatment; Patient 2), 2c pulmonary artery (PA) with an enlarged diameter exceeding the aorta(5 days after treatment; Patient 2), and 3 diffuse poorly defined ground-glass centrilobular nodules(on admission; Patient 3)