Primary Hyperoxaluria (PH)

What Causes Primary Hyperoxaluria (PH)?

PH is a family of rare, genetic disorders that affect the body’s ability to regulate the production of oxalate which can result in kidney damage. The liver normally makes proteins, called enzymes, that prevent the body from making too much oxalate. In PH, the liver doesn’t create enough of this enzyme, or the enzyme doesn’t work properly. To date, experts have identified three different genetic causes of PH.

Type	Genetic mutation	Enzyme deficiency
PH1	AGXT	AGXT
PH2	GRHPR	GR/HPR
PH3	HOGA1	HOGA1

Symptoms

It is important to note that some people with primary hyperoxaluria may not show any symptoms until later in life, while others may experience severe symptoms at a young age. Renal failure can occur as early as infancy while others with PH never develop kidney failure. Although kidney stones, especially kidney stones in childhood, are the most common and often the first symptom of hyperoxaluria, not all individuals with hyperoxaluria will have kidney stones.

The signs and symptoms of primary hyperoxaluria can vary depending on the type of the disorder and the severity of the disease, but if you or a loved one experiences the below signs and symptoms you should further investigate to understand the cause, because it could be hyperoxaluria:

• Failure to thrive – A symptom in children whose weight or rate of weight gain is much lower than that of other children of similar age.
• Kidney failure – Primary hyperoxaluria can cause chronic kidney disease or failure, which can cause fatigue, weakness, and other symptoms.
• Nephrocalcinosis – The accumulation of calcium deposits in the kidneys, also known as nephrocalcinosis, is another common sign of primary hyperoxaluria.
• Blood in the urine – Hematuria, or blood in the urine, can be a sign of kidney damage or injury caused by oxalate crystals.
• High levels of oxalate – Oxalate is a natural product of metabolism in the body, and a urine test may be done to see if an individual has a high level of oxalate.
• Urinary tract infections – People with primary hyperoxaluria may be more prone to urinary tract infections due to the presence of kidney stones and other factors.
• Recurrent kidney stones – One of the most common signs of primary hyperoxaluria is the formation of recurrent kidney stones, which can cause severe pain and discomfort.
• Kidney stones in childhood – While a kidney stone in childhood does not always indicate primary hyperoxaluria, it is a common sign of PH and should be fully investigated by a doctor.

Inheritance and Genetics

A genetic disorder is the result of changes known as pathologic variants in an individual’s DNA. A pathologic variant is a change or “spelling” mistake in the letters of DNA that tell the body how to produce a protein. This section of DNA that contains the instructions for a specific protein is known as a gene.

We have two copies of each gene, one inherited from each parent. PH is inherited in an autosomal recessive pattern, meaning that an affected individual must inherit a pathologic variant or copy of the gene from each parent. The pathologic genetic variants that cause PH control the production of 3 different proteins found primarily in the liver that cause PH1, PH2 and PH3.

Prevalence

The exact prevalence of primary hyperoxaluria is difficult to estimate, but it is believed to be a very rare disorder. According to some estimates, the prevalence of primary hyperoxaluria is about 1 in 59,000 individuals worldwide. However, the prevalence may be higher in certain populations, such as those with a history of consanguinity (marriage between blood relatives) or those with a family history of the disorder.

Read more about primary hyperoxaluria, approved therapies and ongoing clinical trials on the OHF website.

Join the Alliance

Add your voice to a growing global community working to improve the future of hyperoxaluria. Join the Hyperoxaluria Global Alliance.

Source: Oxalosis & Hyperoxaluria Foundation (ohf.org). This information is for educational purposes only and does not replace medical advice.