Liver failure and x-linked immunodeficiency type 47.


Journal

Pediatric transplantation
ISSN: 1399-3046
Titre abrégé: Pediatr Transplant
Pays: Denmark
ID NLM: 9802574

Informations de publication

Date de publication:
12 2020
Historique:
received: 13 11 2019
revised: 29 06 2020
accepted: 06 07 2020
pubmed: 14 8 2020
medline: 21 10 2021
entrez: 14 8 2020
Statut: ppublish

Résumé

Patients with defects in the ATP6AP1 gene have rarely been described. ATP6AP1-related disorders are a subtype of CDG, which result in enzyme deficiencies affecting multiple organ systems ranging from mild to life-threatening. Of the 13 patients described, all had hepatopathy, but this is the first case to be successfully transplanted. We describe two brothers who developed hyperbilirubinemia shortly after birth and progressed to liver failure, case 1 by 12 months of age, with successful transplant 2 years later, and case 2 by 4 months of age, who passed away while awaiting liver transplant. Both boys were found to have a new variant in the ATP6AP1 gene: c.932/p.Leu311Gln. Although the identified ATP6AP1 gene variant was classified as unknown significance at the time, both children's phenotypes fit with what has been described for ATP6AP1-related disorders. Therefore, this result appears to have been diagnostic for both boys. This rare type of CDG, X-linked immunodeficiency type 47 (OMIM #300972), particularly in patients who progress to liver failure requiring transplant, should be included on the differential of liver failure in infants and toddlers, and its gene should be added to the diagnostic workup for such cases.

Identifiants

pubmed: 32790950
doi: 10.1111/petr.13808
doi:

Substances chimiques

ATP6AP1 protein, human 0
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase EC 3.5.1.52
Vacuolar Proton-Translocating ATPases EC 3.6.1.-

Types de publication

Case Reports

Langues

eng

Sous-ensembles de citation

IM

Pagination

e13808

Informations de copyright

© 2020 Wiley Periodicals LLC.

Références

Dimitrov B, Himmelreich N, Hipgrave Ederveen AL, et al. Cutis laxa, exocrine pancreatic insufficiency and altered cellular metabolomics as additional symptoms in a new patient with ATP6AP1-CDG. Mol Gen Metab. 2018;123(3):364-374.
Jansen EJR, Timal S, Ryan M, et al. ATP6AP1 deficiency causes immunodeficiency with hepatopathy, cognitive impairment and abnormal protein glycosylation. Nat Commun. 2016;7:11600.
Witters P, Breckpot J, Foulquier F, et al. Expanding the phenotype of metabolic cutis laxa with an additional disorder of n-linked protein glycosylation. Eur J Hum Genet. 2018;26(5):618-621.
Freeze HH, Schachter H, Kinoshita T. Genetic disorders of glycosylation. Essentials of Glycobiology. 3rdLa Jolla, CA: The Consortium of Glycobiology Editors. 2017. https://www.ncbi.nlm.nih.gov/books/NBK453041/.
Marques-Da-Silva D, Ferreira VDR, Monticelli M, et al. Liver involvement in congenital disorders of glycosylation (CDG). A systematic review of the literature. J Inherit Metab Dis. 2017;40(2):195-207.
Clerc F, Reiding KR, Jansen BC, Kammeijer GS, Bondt A, Wuhrer M. Human plasma protein N-glycosylation. Glycoconj J. 2016;33(3):309-343.

Auteurs

Alexis J Gumm (AJ)

Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.

Donald G Basel (DG)

Division of Pediatric Genetics, Department of Genetics, Medical College of Wisconsin, Milwaukee, WI, USA.

Pooja Thakrar (P)

Division of Pediatric Radiology, Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, USA.

Mariko Suchi (M)

Division of Pediatric Pathology, Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA.

Grzegorz Telega (G)

Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.

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Classifications MeSH