What is Primary Hyperoxaluria?
Primary hyperoxaluria (PH) is a family of severe, rare, genetic liver disorders characterized by overproduction of oxalate, a natural chemical in the body that is normally eliminated as waste through the kidneys. In patients with PH, the kidneys are unable to eliminate the large amount of oxalate that is produced, and the accumulation of oxalate can result in severe damage to the kidneys and other organs.
The three known types of PH (types 1,2,3) each result from a mutation in a specific gene; “no mutation detected” (NMD) PH or idiopathic PH (IPH) is when doctors cannot determine the identity of the gene responsible for the disease. The three genetically known types of PH are: 1,2
- PH1, which is caused by a mutation in the AGXT gene, causing a deficiency of the enzyme alanine:glyoxylate-aminotransferase (AGT)
- PH2, which is caused by a mutation in the GRHPR gene, causing a deficiency of the enzyme glyoxylate/hydroxypyruvate reductase (GR/HPR)
- PH3, which is caused by a mutation in the HOGA1 gene, causing a deficiency of the enzyme 4-hydroxy-2-oxoglutarate aldolase (HOGA)
Download the PH Infographic to learn more about PH, including signs and symptoms, progression of PH and current treatment options.
Signs and Symptoms
Hyperoxaluria occurs when you have too much oxalate in your urine. Oxalate is a natural chemical in your body, and it’s also found in certain types of food. But too much oxalate in your urine can cause serious problems. Patients with decreased renal function may also experience oxalosis, which involves a build-up of oxalate in other organs, such as the bone, skin, heart, and retina, possibly causing other concomitant, debilitating complications.
The three types of PH differ in severity and symptoms. PH1 is the most severe and PH3 is the least severe. To the right is a list of potential signs and symptoms of all forms of PH. Patients with PH3 do not develop systemic oxalosis, and therefore may not experience all of these symptoms.
Often, the first sign of hyperoxaluria is a kidney stone. Symptoms of a kidney stone 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
- Kidney stones
- Kidney damage
- End-stage renal disease and injury to other organs
- Blood in urine
- Urinary tract infections
- Retinal calcifications, resulting in vision problems
- Cardiac failure
- Bone fractures
- Skin calcifications, resulting in painful skin nodules and necrosis
Unmet Medical Need
Currently, there are no approved therapies for the treatment of PH. Untreated PH can eventually damage your kidneys. Oxalosis in its late stages can cause a variety of complications outside the kidney, including bone disease leading to fractures, anemia (lack of red blood cells in your blood, causing tiredness, weakness, and other symptoms), skin ulcers or sores, heart and eye problems, and in children, a failure to develop and grow normally.
Patients with severe PH sometimes must undergo both liver and kidney transplants, which are major surgical procedures, and subsequently must take immunosuppressant drugs for the rest of their lives.
Incidence and Prevalence
- PH has a prevalence of 1-3 cases per million inhabitants and an incidence of 1 in 120,000 live births1
- The estimated genetic prevalence for each type of PH is:1
- 1 in 151,887 for PH1
- 1 in 310,055 for PH2
- 1 in 135,866 for PH3
- PH1 is too often missed in patients with recurrent stone disease or siblings with PH1 and may consequently lead to a high rate of diagnosis in ESRD at an adult age2
- The median age at the first appearance of PH1 symptoms is 5.8 years3
- The median age at diagnosis of PH1 is between 4.2 and 11.5 years, depending on whether nephrocalcinosis (calcification, or hardening of tissues within the body, in the renal parenchyma, the functional part of the kidney) is present3
- Fifty percent of patients with PH1 reach end-stage renal disease (ESRD) by their mid-30s4
- Hopp, K, Cogal, A, Bergstralh, E, et al. Phenotype-genotype correlations and estimated carrier frequencies of primary hyperoxaluria. Journal of the American Society of Nephrology 2015; 26(10):2559-2570.
- van der Hoeven SM, van Woerden CS, Groothoff JW. Primary hyperoxaluria type 1, a too often missed diagnosis and potentially treatable cause of end-stage renal disease in adults: results of the Dutch cohort. Nephrology, Dialysis, Transplantation 2012; 27(10):3855-3862.
- Tang X, Bergstrath EJ, Mehta RA, Vrtiska TJ, Milliner DS, Lieske JC. Nephrocalcinosis is a risk factor for kidney failure in primary hyperoxaluria. Kidney International 2015; 87:623-631.
- Rare Kidney Stone Consortium. Primary hyperoxaluria. 2010. Available at: http://www.rarekidneystones.org/hyperoxaluria/physicians.html. Accessed July 6, 2017.