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.

Sorbitol Is a Severity Biomarker for PMM2‐CDG with Therapeutic Implications

“…Disease severity was assessed by Nijmegen Progression CDG Rating Scale (NPCRS), most severe = 82; mild = 0–14, moderate = 15–25, and severe = >26 12,13 . P1 was previously reported by Qian et al 14 and P4 and P5 by Jaeken et al 15 Patient 1, enrolled in a single investigational new drug (IND) clinical trial was additionally evaluated by the International Cooperative Ataxia Rating Scale (ICARS) 16 Investigation New Drug Protocol (IND) PMM2‐CDG‐001 . ICARS assesses limb ataxia, dysarthria, posture and gait disturbances, and oculomotor disorders; 0 = normal to 100 = most severe.…”

Recurrent fetal truncus arteriosus associated with PMM2‐CDG

“…The recent article "Vascular ring anomaly in a patient with phosphomannomutase 2 deficiency: a case report and review of the literature" published in JIMD Reports by Quian et al suggests that congenital defects of glycosylation (CDG) should be part of the differential diagnosis in patients with cardiac malformations. 1 We believe our case is relevant in this context.…”