Noncompaction of the ventricular myocardium and hydrops fetalis in cobalamin C disease

Abstract

We reported the first patient with early onset cobalamin C disease (cblC) who presented with non-immune hydrops fetalis, who also had left ventricular noncompaction (LVNC) and heart failure in the neonatal period. After metabolic management and ionotrophic support, her left ventricular function improved. At 30 months, the last age of evaluation at our center, the apex of the left ventricle was globular but cardiac function was within normal limit on digoxin therapy. A cardiac MRI to more precisely characterize the ventricular myocardium has not yet been performed. Although beyond the scope of a case report, the questions raised regarding theoretical explanations for the natural history and disease course of LVNC in cblC and also relationship of LVNC to other neuromuscular disorders such as Duchenne’s muscular dystrophy are intriguing and will remain as challenges for future research. Drs. Finsterer and Stollberger affirm that “LVHT in cobalamin-C-deficiency was found only in a limited number of patients with a specific mutation”. We disagree with this statement. The only systematic echocardiographic survey of cardiac disease in a cohort of cblC patients was reported by Profitlich et al (1) in a small group of 10 patients: 3 patients (33%) had LVNC. Of specific relevance to Drs. Finsterer and Stollberger’s comment is that the three patients with LVNC reported by Profitlich et al harbored a total of 4 distinct MMACHC mutations, suggesting that there is not a specific mutation seen in the reported cblC patients with LVNC. LVNC is recognized as a genetically heterogeneous disease, associated with variable clinical symptoms (2). We offered a hypothesis to explain a possible correlation between LVNC and cblC disease, not a statement of causal relationship as claimed by Drs. Finsterer and Stollberger, but do agree that definitive studies examining LVNC in the setting of MMACHC deficiency need to be rigorously assessed. The detailed cardiovascular and echocardiographic characterization of larger numbers of cblC patients, with an extension into relevant animal models, would be one approach to assess whether a cause and effect relationship between LVNC and MMACHC deficiency exists.