tellmegen logo
-10% on Individual and Children's Kits. Code: ADN10DNA_testBUY NOW!



Primary hyperoxaluria type 1 (PH1)

Primary hyperoxaluria type 1 (PH1) is a rare disorder of glyoxylate metabolism characterized by the accumulation of oxalate due to a deficiency of the peroxisomal hepatic enzyme L-alanine: glyoxylate aminotransferase (AGT). Clinical presentation is variable, ranging from occasional symptomatic nephrolithiasis to nephrocalcinosis and end-stage renal disease with systemic involvement.

PH1 is due to a defect of the peroxisomal hepatic enzyme AGT caused by mutations in the AGXT gene (2q37.3). The defect in AGT, which normally converts glyoxylate to glycine, results in an increase of the glyoxylate pool, which is converted to oxalate (poorly soluble) and glycolate (without associated pathology).

The prevalence of PH1 reported in Europe ranges from 1/333,000 – 1/1,000,000. Higher values are reported in specific populations with a high rate of consanguinity.

There exists an important heterogeneity in the clinical presentation and onset of PH1. The severe infantile form is characterized by a failure to thrive, nephrocalcinosis with or without nephrolithiasis and early end-stage renal failure. An onset in childhood and adolescence is often characterized by recurrent urolithiasis (with or without nephrocalcinosis) and progressive renal failure. The late onset form is mostly characterized by occasional renal stones with a disease onset in adulthood, but acute renal failure caused by bilateral obstruction of the kidneys by oxalate stones may occur. Other manifestations include urinary tract infections, dysuria and hematuria. The ongoing systemic oxalosis also may lead to other clinical manifestations such as cardiac conduction defects, vascular calcification with distal gangrene, disturbed vision, specific brown colored retinal deposits, skin nodules, joint involvement and bone disease leading to fractures in long-term dialysis-dependent patients.

Clinical diagnosis is suspected on clinical features along with pure calcium oxalate monohydrate stone composition and confirmed by urine oxalate: creatinine ratio, molecular genetic testing and infrequently by AGT catalytic activity from liver biopsy.

Transmission of PH1 is autosomal recessive and heterozygotes are asymptomatic. Genetic counseling should be offered to affected individuals and at-risk family members.

Early vigorous treatment is essential for maintaining renal function. Treatment involves minimizing calcium oxalate deposition before advanced renal failure by the maintenance of a high urine output, vitamin B6 (pyridoxine), and calcium-oxalate crystallization inhibitors (citrate, pyrophosphate, and magnesium). Combined liver-kidney transplantation should be considered in most patients as a preemptive procedure, and any kind of dialysis should be avoided or at least minimized. Adeno-associated viral vector of serotype 5 containing the human alanine-glyoxylate aminotransferase gene or cell therapy may be available for the treatment of primary hyperoxaluria in Europe in the future.

Prognosis is very poor if manifest PH1 is left untreated. In the future, the prognosis may be improved by cell/gene therapy or the use of chaperone molecules.


  • AGXT