Primary hyperoxaluria type 1 in developing countries: novel challenges in a new therapeutic era

Abstract

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inborn error of metabolism characterized by marked hepatic overproduction of oxalate due to deficiency of hepatic peroxisomal alanine-glyoxylate aminotransferase caused by AGXT gene mutation. One major hallmark of PH1 in developed as well as developing countries (DC) is the diagnostic delay. Notably in DC, where the disease is most prevalent and probably underdiagnosed, there are many challenges in PH1 diagnosis and management, with economic constrains and ethical concerns. This has led to the existing gap in the management of PH1 between developed and DC, which is expected to further deepen with the advent of novel therapeutic agents unless appropriate actions are taken. Until recently, treatment possibilities were limited to supportive measures. Thanks to a better understanding of the molecular basis of the disease a number of new therapies are developed, or being developed, leading to profound changes in management strategies. In this review we discuss the current situation of PH1 in DC as well as the accessibility challenges and the advantages of using promising novel therapeutics to bridge the currently existing gap. We also provide an overview of an integrated approach to ensure equitable access of sustainable therapeutics to PH1 patients in DC. This is expected to reduce global PH1 healthcare disparities, improve its standard of care and reduce disability linked to extrarenal complications of PH1 by implementing personalized medicine.

Hyperoxaluries primitives et secondaires

“…Dans le champ des maladies rares, les questionnements éthiques et médico-économiques sont essentiels et les HP ne font pas exception. On peut regretter, comme dans d'autres maladies orphelines, le fossé qui existe entre pays développés et pays en voie de développement pour le diagnostic, l'accès aux tests génétiques et bien évidemment l'accès aux thérapies innovantes [13]. La disponibilité en Europe et aux États-Unis des très coûteux ARNi ne fera qu'accentuer ce problème, alors que l'HP1 est un véritable fléau dans certains pays en voie de développement.…”

Primary hyperoxaluria: Description of a new oral finding and review of literature

“…4 The disease seems to be more common in isolated populations where consanguineous marriage is frequently practiced, especially in the Middle East and North Africa. 5,6 The clinical presentations of PH vary greatly depending on the type and the severity of enzyme defect. In the main, PH presents as recurrent nephrolithiasis and progressive nephrocalcinosis leading to renal damage due to deposition of calcium-oxalate into renal tissues.…”

“…The exact prevalence of PH is not known, but it is estimated to range from 1 to 3 per million population 4 . The disease seems to be more common in isolated populations where consanguineous marriage is frequently practiced, especially in the Middle East and North Africa 5,6 …”

Nedosiran Safety and Efficacy in PH1: Interim Analysis of PHYOX3

“…If left untreated, severe CKD will eventually impair oxalate excretion to an extent that it causes systemic storage of oxalate in various tissues (such as skin, eyes, bones, and heart), causing life-threatening and disabling multiorgan disease called systemic oxalosis. 1 , 4 , 5 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 …”