Primary hyperoxaluria

Primary hyperoxaluria is a rare inherited condition in which the body makes too much oxalate and excretes far more of it in the urine than normal, so that oxalate stones are common. It is an autosomal recessive disease, meaning a child must receive a mutated copy of the gene from each parent, while the parents usually show no signs themselves. The cause is a set of genetic defects that lead to overproduction of oxalate, which separates it from secondary hyperoxaluria, where the oxalate load comes from diet, intestinal absorption or excess oxalate precursors. A single kidney stone in a child, or repeated stones in an adult, is often the first warning sign, and other features include urinary tract infections, abdominal or flank pain, blood in the urine, chronic kidney disease and kidney failure. Stones can obstruct the urinary tract and damage the kidneys, often from the teenage years to early adulthood, and once kidney function fails oxalate can be deposited in bone, joints and bone marrow, a state called oxalosis. Three main types are described: types 1, 2 and 3 are linked to mutations in the AGXT, GRHPR and HOGA1 genes, which act in the metabolism of glyoxylate, the precursor of oxalate. Type 1 is the most common and fastest progressing form, accounting for about 80 percent of diagnosed cases, with types 2 and 3 about 10 percent each. Diagnosis rests on stone and urine analysis to exclude secondary causes, with genetic testing for a definitive answer. Management includes more water and alkalinised urine, and pyridoxine (vitamin B6) helps about a third of people with type 1. The RNA interference drugs lumasiran, approved in the European Union and United States in November 2020, and nedosiran, approved in the United States in September 2023, are used against type 1.