What is Primary Hyperoxaluria?
Primary Hyperoxaluria (PH) is a family of ultra-rare, life-threatening genetic liver disorders that cause complications in the kidneys. There are three known types of PH, each resulting from a mutation in one of three different genes. These genetic mutations cause enzyme deficiencies that manifest in the overproduction of a substrate called oxalate. Abnormal production and accumulation of oxalate leads to recurrent kidney stones, nephrocalcinosis and chronic kidney disease that may progress to end-stage renal disease requiring regular dialysis and a dual liver-kidney transplant.
|Subtype||Mutated Gene||Deficient Enzyme|
|PH1||AGXT||alanine-glyoxylate aminotransferase (AGT)|
|PH2||GRHPR||glyoxylate reductase/hydroxypyruvate reductase (GR/HPR)|
|PH3||HOGA1||4-hydroxy-2-oxoglutarate aldolase (HOGA)|
|Idiopathic PH (IPH) or No Mutation Detected (NMD) PH||Unknown||Unknown|
Signs and Symptoms
Often, the first signs of Primary Hyperoxaluria are caused by kidney stones (typically even a single in infants and children as well as recurrent stones in adolescents and adults). Symptoms of kidney stones can include:
- Severe or sudden back pain
- Pain in the area below the ribs on the back (flank) that doesn’t go away
- Blood in the urine
- Frequent urge to urinate
- Pain when urinating
- Chills or fever
Decreased renal function associated with PH may also lead to end-stage renal disease and systemic oxalosis. Systemic oxalosis involves a build-up of oxalate in other regions of the body causing a variety of complications including:
- Bone disease leading to fractures
- Anemia (lack of red blood cells causing tiredness, weakness and other symptoms)
- Skin ulcers or sores
- Heart problems
- Eye problems
- Failure to develop and grow normally in children
Progression of PH
Note: PH can have varying levels of severity depending on the type
Download the PH Infographic to learn more about PH, including signs and symptoms, progression of PH, and current treatment options.
The estimated genetic prevalence rates for PH imply more than 16,000 patients in the United States and European Union have the disease:
- PH1: 1 in approximately 120,000
- PH2: 1 in approximately 197,000
- PH3: 1 in approximately 79,000
Genetic studies suggest that Primary Hyperoxaluria is likely under diagnosed, especially PH3.
Age at first onset of symptoms and age at diagnosis can range from newborn to adulthood.
Unmet Medical Need
Currently, there is no approved therapy specifically for the treatment of PH. Patients are limited to using hyperhydration and medication to attempt to increase solubility of oxalate in urine. Despite these interventions, oxalate may continue to accumulate in the kidneys, causing damage. Patients with severe PH may require regular dialysis and a dual liver-kidney transplant. Transplants are major surgical procedures, and subsequently patients must take immunosuppressant drugs for the rest of their lives.