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

• Published in: International journal of molecular sciences Vol. 24; no. 8; p. 7449
• Main Authors: Semenova, Natalia, Shatokhina, Olga, Shchagina, Olga, Kamenec, Elena, Marakhonov, Andrey, Degtyareva, Anna, Taran, Natalia, Strokova, Tatiana
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2023; MDPI
• Subjects: ATP6AP1; Bacterial infections; Blood proteins; Case Report; cholestasis; Congenital Disorders of Glycosylation - genetics; Congenital Disorders of Glycosylation - metabolism; Genetic disorders; Glycosylation; Health aspects; Humans; Infant; Liver; Liver Transplantation; Male; Tacrolimus; Transferrin - metabolism; Transplantation; Vacuolar Proton-Translocating ATPases - metabolism; X-linked primary immunodeficiency; Russia; ATP6AP1; X-linked primary immunodeficiency; cholestasis; liver transplantation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24087449

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 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.