Primary Hyperoxaluria Type 3 Can Also Result in Kidney Failure: A Case Report

Abstract

Primary hyperoxaluria (PH) is a group of genetic disorders that result in an increased hepatic production of oxalate. PH type 3 (PH3) is the most recently identified subtype and results from mutations in the mitochondrial 4-hydroxy-2-oxoglutarate aldolase gene (HOGA1). To date, there have been 2 cases of kidney failure reported in PH3 patients. We present a case of a young man with a history of recurrent urinary tract infections and voiding dysfunction who developed kidney failure at 33 years of age. He developed a bladder stone and bilateral staghorn calculi at 12 years of age. Initial metabolic evaluation revealed hyperoxaluria with very low urinary citrate excretion on multiple measurements for which he was placed on oral citrate supplements. Further investigation of the hyperoxaluria was not completed as the patient was lost to follow-up observation until he presented at 29 years of age with chronic kidney disease stage 4 (estimated glomerular filtration rate 24mL/min/1.73m²). Hemodialysis 3 times a week was started at 33 years of age, and subsequent genetic testing revealed a homozygous HOGA1 mutation (C.973G>A p.Gly325Ser) diagnostic of PH3. The patient is currently being evaluated for all treatment options including possible liver/kidney transplantation. All cases of a childhood history of recurrent urinary stone disease with marked hyperoxaluria should prompt genetic testing for the 3 known PH types. Hyperhydration and crystallization inhibitors (citrate) are standard of care, but the role of RNA interference agents for all 3 forms of PH is also under active study.

Keywords: Case report; PH3; hyperoxaluria; kidney failure; kidney stone; mitochondrial 4-hydroxy-2-oxoglutarate aldolase (HOGA1); mutation; oxalate; primary hyperoxaluria (PH); urinary tract infections (UTIs).

Figure 1:

Algorithm for diagnostic evaluation of primary hyperoxaluria in affected individual * Random oxalate/creatinine ratios vary significantly by age. Consult pediatric reference range tables or interpretation. ** Since it is often difficult to interpret the treatment impact for secondary causes when GFR is markedly reduced, genetic testing should also be strongly considered in this group of patients if the cause remains unclear. *** Interpretive report includes an overview of results and of their significance along with a recommendation for confirmatory molecular testing for either AGXT, GRHPR, or HOGA1 Based in part on Milliner.