Liver transplantation recovers hepatic N-glycosylation with persistent IgG glycosylation abnormalities: Three-year follow-up in a patient with phosphomannomutase-2-congenital disorder of glycosylation

Abstract

Phosphomannomutase-2-congenital disorder of glycosylation (PMM2-CDG) is the most common CDG and presents with highly variable features ranging from isolated neurologic involvement to severe multi-organ dysfunction. Liver abnormalities occur in in almost all patients and frequently include hepatomegaly and elevated aminotransferases, although only a minority of patients develop progressive hepatic fibrosis and liver failure. No curative therapies are currently available for PMM2-CDG, although investigation into several novel therapies is ongoing. We report the first successful liver transplantation in a 4-year-old patient with PMM2-CDG. Over a 3-year follow-up period, she demonstrated improved growth and neurocognitive development and complete normalization of liver enzymes, coagulation parameters, and carbohydrate-deficient transferrin profile, but persistently abnormal IgG glycosylation and recurrent upper airway infections that did not require hospitalization. Liver transplant should be considered as a treatment option for PMM2-CDG patients with end-stage liver disease, however these patients may be at increased risk for recurrent bacterial infections post-transplant.

Keywords: CDG; Glycosylation; Immunoglobulin; Infection; Liver transplantation; PMM2-CDG; Phosphomannomutase.

Figure 1.

Clinical photographs of the PMM2-CDG patient before (A) and 1.5 year after (B) liver transplantation. Prior to transplant, she suffered from complications of cirrhosis, including ascites and spontaneous bacterial peritonitis, and was developmentally stagnant. After transplant, she progressed in her developmental milestones and acquired good head control and improved motor coordination. Figure 1C. HE staining of the liver explant. Anterior and posterior views of the explanted liver, showing diffuse macronodular cirrhosis.

Figure 2.

(A) The explanted liver from the PMM2-CDG patient shows the formation of numerous nodules, consistent with established cirrhosis (hematoxylin-eosin stain, original magnification x20). (B) A focus of glycogen-rich hepatocytes characterized by abundant clear cytoplasm (left side of image) and minimal macrovesicular steatosis (right side of image) (hematoxylin-eosin stain, original magnification x100).