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

Int J Mol Sci. 2023 Apr 18;24(8):7449. doi: 10.3390/ijms24087449.

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.

Keywords: ATP6AP1; X-linked primary immunodeficiency; cholestasis; liver transplantation.

Publication types

  • Case Reports

MeSH terms

  • Congenital Disorders of Glycosylation* / genetics
  • Congenital Disorders of Glycosylation* / metabolism
  • Glycosylation
  • Humans
  • Infant
  • Liver Transplantation*
  • Male
  • Tacrolimus
  • Transferrin / metabolism
  • Vacuolar Proton-Translocating ATPases* / metabolism

Substances

  • Tacrolimus
  • Transferrin
  • ATP6AP1 protein, human
  • Vacuolar Proton-Translocating ATPases

Grants and funding

The work was funded by a state assignment of the Ministry of Science and Higher Education of the Russian Federation. The funder had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.