Clinical Presentation of a Patient with a Congenital Disorder of Glycosylation, Type IIs (ATP6AP1), and Liver Transplantation

Abstract

The congenital disorder of glycosylation type IIs (ATP6AP1-CDG; OMIM# 300972) is a rare X-linked recessive complex syndrome characterized by liver dysfunction, recurrent bacterial infections, hypogammaglobulinemia, and defective glycosylation of serum proteins. Here, we examine the case of a 1-year-old male patient of Buryat origin, who presented with liver dysfunction. At the age of 3 months, he was hospitalized with jaundice and hepatosplenomegaly. Whole-exome sequencing identified the ATP6AP1 gene missense variant NM_001183.6:c.938A>G (p.Tyr313Cys) in the hemizygous state, which was previously reported in a patient with immunodeficiency type 47. At the age of 10 months, the patient successfully underwent orthotopic liver transplantation. After the transplantation, the use of Tacrolimus entailed severe adverse effect (colitis with perforation). Replacing Tacrolimus with Everolimus led to improvement. Previously reported patients demonstrated abnormal N- and O-glycosylation, but these data were collected without any specific treatment. In contrast, in our patient, isoelectric focusing (IEF) of serum transferrin was performed only after the liver transplant and showed a normal IEF pattern. Thus, liver transplantation could be a curative option for patients with ATP6AP1-CDG.

Expanding the phenotype and metabolic basis of ATP6AP2-congenital disorder of glycosylation in a Chinese patient with a novel variant c.185G>A (p.Gly62Glu)

“…In addition, organ transplantation, such as liver transplantation for end-stage cirrhosis, was recommended recently. Successful liver transplantation was reported in ATP6AP1-CDG, MPI-CDG, and PMM2-CDG (Janssen et al, 2014;Alharbi et al, 2023;Semenova et al, 2023;Tahata et al, 2023). After liver transplantation in the patients, not only the specific clinical presentation was improved, but the abnormal glycosylation was also restored.…”