Primary Hyperoxaluria in Macedonian Children

Background: Primary hyperoxalurias (PH) are hereditary disorders of glyoxylate and oxalate metabolism with consecutive nephrolithiasis, nephrocalcinosis and progressive renal damage resulting in end stage kidney disease and systemic oxalosis.

Objective: The aim of this retrospective study was to analyze the clinical features, biochemical parameters, genetic findings and outcome in Macedonian children with primary hyperroxaluria.

Methods: PH was defined if the urinary oxalate levels were > 1.0 mmol/1.73m²/d. Secondary causes were excluded on the basis of dietary history, physical examination and laboratory tests. Urinary excretion of glycolate and glycerate was determined within the same samples. 24-hour urine samples were collected for testing pyridoxine sensitivity while in anuric patients plasma oxalate concentration were measured before and after pyridoxine challenge. Mutational analysis of the respective PH1/2/3 genes was performed.

Results: In the period 1995-2018 there were 10 patients with PH (In 6 confirmed with mutational analysis of the AGXT gene). There were no patients with PH2/3. The youngest patient at diagnosis was 4 months old and the oldest 18 years. Four patients progressed to ESKD and one died. Three patients were sensitive to pyridoxine. One patient had nephrolithiasis which was initially considered as a consequence of ureteropelvic junction obstruction, but metabolic investigation revealed hyperoxaluria, hyperlglycolaturia and normalization of urinary oxalate excretion under pyridoxine treatment.

Conclusions: Macedonian PH children were diagnosed late in the course of the disease when progressive kidney damage ensued. There were no cases of PH2 and PH3. It seems that yet unidentified genes are responsible for PH in Macedonian children. One should implement mandatory urinary oxalate screening in all children with urolithiasis/nephrocalcinosis in order to initiate early and aggressive conservative management to prevent systemic oxalosis.