Other names: Oxalosis; PH1

Primary hyperoxaluria type 1 (PH1) is an ultra-rare genetic disease characterized by oxalate overproduction.

PH1 is an autosomal recessive disorder of glyoxylate metabolism, where hepatic detoxification of glyoxylate is impaired due to mutation of the AGXT gene, which encodes the liver peroxisomal alanine-glyoxylate aminotransferase (AGT) enzyme, resulting in excessive oxalate production. The excess production of oxalate results in the deposition of calcium oxalate crystals in the kidneys and urinary tract and can lead to the formation of painful and recurrent kidney stones which can progress to kidney failure.

PH1 is associated with a progressive decline in kidney function, which exacerbates the disease as the excess oxalate can no longer be effectively excreted, resulting in subsequent accumulation and deposition of oxalate in bones, eyes, skin, and heart, leading to severe illness and death.

Management options for PH1 include hyperhydration, crystallization inhibitors and, in a minority of patients with a specific genotype, pyridoxine (vitamin B6). These measures help to delay inevitable progression to kidney failure.

Oxlumo (lumasiran) is the the first FDA approved therapy for the treatment of PH1. It works by reducing the hepatic levels of the GO enzyme, thereby depleting the substrate necessary for oxalate production.

Drugs used to treat Primary Hyperoxaluria