Vascular ring anomaly in a patient with phosphomannomutase 2 deficiency: A case report and review of the literature

Abstract

Background: Congenital disorders of glycosylation (CDG) are a group of metabolic disorders well known to be associated with developmental delay and central nervous system anomalies. The most common CDG is caused by pathogenic variants in the phosphomannomutase 2 gene (PMM2), which impairs one of the first steps of N-glycosylation and affects multiple organ systems. Cardiac involvement can include pericardial effusion, cardiomyopathy, and arrhythmia, while an association with cardiovascular congenital anomalies is not well studied. Case summary: We report a 6-year-old individual who initially presented with inverted nipples, developmental delay, and failure to thrive at 3 months of age. At 4 months, due to feeding problems, swallowing exam and echocardiography were performed which revealed a vascular ring anomaly based on a right aortic arch and aberrant left subclavian artery. Subsequent whole exome gene sequencing revealed two pathogenic PMM2-CDG variants (E139K/R141H) and no known pathogenic mutations related to congenital heart defect (CHD). Discussion: This is the first report of vascular ring anomaly in a patient with PMM2-CDG. We conducted a literature review of PMM2-CDG patients with reported CHD. Of the 14 patients with PMM2-CDG and cardiac malformation, the most common CHD's were tetralogy of Fallot, patent ductus arteriosus, and truncus arteriosus. The potential important link between CDG and CHD is stressed and discussed. Furthermore, the importance of multidisciplinary care for CDG patients including early referral to pediatric cardiologists is highlighted.