2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Donor Organ Failure: The Importance of Donor Heterozygosity in a Case of Primary Hyperoxaluria Type 1

Pdf Summary

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by the buildup of oxalate crystals in affected organs. It is caused by pathogenic variants in the AGXT gene. The only curative treatment for PH1 is liver and kidney transplantation. Heterozygotes for PH1 typically do not develop renal failure, but they can have reduced hepatic AGT enzyme activity.<br /><br />This case report describes a 13-year-old girl from Saudi Arabia diagnosed with PH1 at the age of 6. She underwent a liver transplant from an unrelated donor at the age of 10. However, she developed liver oxalate and her hyperoxaluria did not improve after the transplant. Genetic testing revealed that the donor liver had a heterozygous pathogenic variant in the AGXT gene. This suggests that using a liver from a heterozygous carrier of the AGXT pathogenic variant can contribute to transplant failure in PH1 patients. In highly consanguineous populations like Saudi Arabia, genetic screening of donors before liver transplantation may be necessary to prevent this complication.<br /><br />The patient's physical exam revealed various abnormalities, including splenomegaly, bony abnormalities, and liver and kidney dysfunction. Liver biopsy showed ductopenia, cirrhosis/bridging fibrosis, and hemosiderin deposition. Genetic testing confirmed the presence of a pathogenic variant in the AGXT gene in the donor liver.<br /><br />In conclusion, this case highlights the importance of considering pre-emptive transplantation in PH1 patients with progressive renal failure and the potential complications of using donor livers with pathogenic variants in the AGXT gene. Genetic screening of donors may be necessary to improve transplant outcomes in PH1 patients.

Asset Subtitle

Presenting Author - Kathryn Leal, MS, CGC; Co-Author - David Rodriguez-Buritica, MD; Co-Author - Essam Imseis, MD; Co-Author - Amr Elgehiny, MD;

Meta Tag

Genotype-Phenotype Correlations

Inheritance Patterns

Mapping Complex Traits

Pathology

Transplantation

Co-Author David Rodriguez-Buritica, MD

Co-Author Essam Imseis, MD

Co-Author Amr Elgehiny, MD

Presenting Author Kathryn Leal, MS, CGC

Keywords

Primary hyperoxaluria type 1

PH1

genetic disorder

oxalate crystals

AGXT gene

liver transplantation

kidney transplantation

heterozygotes

renal failure

hepatic AGT enzyme activity