ESPN 53rd Annual Meeting

ESPN 2021


 
Successful early treatment with stiripentol in a patient with primary hyperoxaluria type 1
PRISCILLIA VIOLIER 1 OLIVIA BOYER 2 ROMAIN BERTHAUD 2 CHARLOTTE SAMAILLE 1 ROBERT NOVO 1 GUILLAUME DORVAL 2

1- NEPHROLOGIE PéDIATRIQUE, UNIVERSITé DE LILLE, LILLE, FRANCE
2- NéPHROLOGIE PéDIATRIQUE, MARHEA, INSTITUT IMAGINE, UNIVERSITé DE PARIS, HôPITAL NECKER - ENFANTS MALADES, APHP, PARIS, FRANCE
 
Abstract:

Primary hyperoxaluria type 1 (HP1) is a rare autosomal recessive disorder caused by biallelic pathogenic AGXT variants. The gene defect results in dysfunction of the liver-specific peroxisomal enzyme alanine amino-transferase (AGT) and consequently nephrocalcinosis, kidney stones, kidney failure and systemic oxalosis despite supportive care. Until recently, the only specific treatment was liver-kidney transplantation. Therapeutic prospects, notably with interfering RNA, would aim at reducing the substrate by upstream oxalate enzyme blockade. Stiripentol is an anti-epileptic drug registered in pediatric Dravets syndrome and well-tolerated in young children. It inhibits the lactate dehydrogenase 5 enzyme, the key enzyme of the last step in the hepatic production of oxalate. It is therefore hypothesized to reduce hepatic oxalate production and urinary excretion, thereby preventing progression to kidney failure and systemic oxalosis in HP1. We report the case of a 18 month-old girl diagnosed with HP1 with bilateral kidney stones who received stiripentol from the age of 21 months with adjunctive measures. Her urinary oxalate/creatinine ratio quickly decreased from 0.48 to 0.07 mmol/mmol and was followed by complete normalization of the kidney ultrasound after 11 months of treatment. No side effect was noted. We suggest considering a trial of stiripentol in children with HP1, alone or in combination with other therapeutic strategies such as RNA interfering drugs where available.