Primary hyperoxaluria type 3: from infancy to adulthood in a genetically unique cohort

Area of Science:

• Genetics
• Nephrology
• Rare Diseases

Background:

• Primary hyperoxaluria type 3 (PH3) is a rare autosomal recessive disorder.
• It is caused by genetic variants in the 4-hydroxy-2-oxoglutarate aldolase (HOGA-1) gene.
• This study focuses on the natural history of PH3 within a specific, genetically isolated population.

Purpose of the Study:

• To describe the natural history of PH3 in a cohort of 16 patients.
• To determine the carrier frequency of PH3-associated HOGA-1 variants in a genetically isolated population.
• To identify couples at risk for having children with PH3.

Main Methods:

• Retrospective single-center study of PH3 patients from 2003-2023.
• Collected demographic, clinical, radiographic, genetic, and biochemical data.
• Conducted genetic population screening in four villages to assess carrier frequency.

Main Results:

• Sixteen patients with biallelic HOGA-1 pathogenic variants were identified (15 Druze, 1 Jewish).
• All symptomatic patients exhibited signs of nephrolithiasis; one progressed to CKD stage 5.
• Carrier screening revealed a 1:13 carrier rate in the studied isolated population.

Conclusions:

• PH3 is highly prevalent in this unique cohort, though likely underdiagnosed due to a mild disease course.
• A high carrier rate necessitates awareness and potential genetic counseling.
• While no specific therapy exists, early diagnosis aids in managing kidney stone disease and preventing unnecessary investigations.