Introduction Oxalate and PH1 Consequences Signs Symptoms INHERITANCE

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ABOUT PRIMARY HYPEROXALURIA TYPE 1 (PH1):

What is primary hyperoxaluria type 1 (PH1)?

A PH1 diagnosis can be overwhelming. It's OK to have questions. The good news is, even though it's a rare condition, you're not alone. Learn about how PH1 affects the body, genetic testing, and more.

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How prevalent is PH1?

Primary hyperoxaluria is a rare, inherited, autosomal recessive, and progressive disease that causes the overproduction of oxalate. Normally, oxalate is present only in small amounts, is not used by the body for anything, and is primarily eliminated by the kidneys.

Roughly 70% to 80%

Roughly 70% to 80% of all people with primary hyperoxaluria have PH1—the most common and severe type.

Approximately 1 to 3 of every million people

Approximately 1 to 3 of every million people in Europe and North America have PH1. There is an even higher prevalence of the disease in the Middle East and North Africa regions.

It is estimated that about half

It is estimated that about half of all people with PH1 may be undiagnosed. This means there are people who have PH1 but have not yet been diagnosed with the disease.

The earliest sign

The earliest sign of PH1 is often kidney stones that form due to oxalate overproduction in the liver. Kidney stones are the most common symptom of PH1, although not every patient may have kidney stones. Once in the kidneys, oxalate combines with calcium in urine. When oxalate and calcium combine, crystals are formed. Over time, more and more crystals are made that get trapped in the kidneys. Crystals can clump together to create hard masses (kidney stones), or they can be deposited in the kidneys themselves (nephrocalcinosis).

The buildup of crystals in the kidneys can lead to chronic kidney disease (CKD) or even kidney failure. As kidney function worsens, the kidneys are no longer able to remove oxalate properly, and the oxalates get deposited in other parts of the body and cause damage.

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PH1 Perspectives: Describing PH1

https://vimeo.com/405488810

Patients and Caregivers Describe Primary Hyperoxaluria Type 1

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What causes PH1?

Normally, glycolate oxidase (GO) and alanine:glyoxylate aminotransferase (AGT) enzymes in the liver work together to regulate levels of oxalate. In PH1, AGT is broken, and GO continues to work and make the building blocks for oxalate. This leads to the overproduction of oxalate.

Watch how this happens, below:

https://vimeo.com/405479964##timer=0##timer=101.5

About Primary Hyperoxaluria Type 1 - Video 1

Oxalate is a waste product that cannot be further broken down or used by the body, and is primarily eliminated by the kidneys.

Read It For Yourself

Normal Process in Liver for Glycolate Oxidase and Alanine Glyoxylate Aminotransferase

GO and AGT normally work together

GO makes a substance that acts as a building block that AGT transforms into an amino acid for your body to use.

Abnormal Process in Liver for Glycolate Oxidase and Alanine Glyoxylate Aminotransferase

When AGT is broken, GO can cause problems

In PH1, AGT is broken, and GO continues to work and make the building blocks for oxalate. This leads to the overproduction of oxalate.

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How does PH1 affect the kidneys?

In PH1, oxalate is constantly being overproduced by the liver, and the kidneys cannot keep up with removing it. Watch the video below to understand how damage can occur:

https://vimeo.com/405479964##timer=102##timer=160

About Primary Hyperoxaluria Type 1 - Video 2

Oxalate is constantly overproduced and can cause continuous damage that gets worse over time. Diagnosing PH1 as early as possible can help you take steps to manage it.

Read It For Yourself

Once in the kidneys, oxalate combines with calcium in your urine to form calcium oxalate crystals. These crystals can damage your kidneys and affect their ability to filter waste in two ways:

Crystals clump together to create hard masses (kidney stones, also called nephrolithiasis)

Crystals deposit in the kidneys themselves (called nephrocalcinosis)

People with PH1 may have both kidney stones and nephrocalcinosis. But with or without symptoms, oxalate is constantly being overproduced and may continually be doing damage. The damage PH1 causes happens at different rates in different people and it can be permanent.

The kidney damage from PH1 affects the kidneys' ability to filter waste from your blood and to create urine. Over time, the buildup of crystals in the kidneys leads to kidney failure, which is also known as end-stage kidney disease (ESKD).

As kidney function worsens, the kidneys are no longer able to eliminate oxalate properly and it starts to spread and form crystals throughout the body. This process is called systemic oxalosis. Crystals cause damage where they are deposited. This can occur in multiple organs in the body, including the bones, eyes, skin, and heart.

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What are the common signs of PH1?

Although kidney stones are the most common, and often the first sign of PH1, not all people with PH1 will have stones. When you have PH1, your kidneys are at risk for damage even if you are not getting stones.

In fact, PH1 may present in a number of ways:

Having any kidney stones,
even only one, as a child

Having repeated kidney stone episodes (recurrent kidney stones)

Nephrocalcinosis (finding crystals in kidney tissue during a renal evaluation)

End-stage kidney disease (kidney failure)

Failure to thrive
(not growing sufficiently as a baby)

These are not all the possible signs, symptoms, or complications of PH1, and not all people with PH1 exhibit them at the same times. Having one of these signs or symptoms does not necessarily mean that you or a loved one have PH1. Your doctor is your most important source of information if you ever have questions about your health.

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PH1 Perspectives: How I got my PH1 diagnosis

https://vimeo.com/405484174

Hear Parents Describe the Path to Their Children's Primary Hyperoxaluria Type 1 Diagnoses

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DIG DEEPER

The signs of PH1 may not always be noticeable; they can go unrecognized or be confused with the signs of other disorders. Adults with PH1 can wait several years or longer after experiencing their first symptom and before receiving a PH1 diagnosis. However, even if there are no noticeable signs of PH1 in a person with the disease, oxalate is constantly being overproduced. That’s one reason why it’s important to diagnose PH1 early.

If you have noticed one or more signs of PH1, including having a family history of the disease, you may want to talk to a healthcare provider. They can help you determine if you should consult with a nephrologist (kidney specialist).

Testing as early as possible for PH1 may shorten the often long time it takes for people to get diagnosed.

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There was just blood in his urine.
He had
no other symptoms, but you could see that he was in pain. I remember he had a lot of stones in his kidney when he first got diagnosed.

Pat C.

Mom of an adult with PH1

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Build a personalized PH1 discussion guide

If you or a relative of yours has a history of kidney stones, or other signs that make you curious about PH1, you can answer 6 quick questions to receive a personalized discussion guide. Once completed, you can bring it to your healthcare provider to discuss if you or your loved one should be tested for PH1.

Or you can download, print, and answer the PH1 discussion guide questions.

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How many kidney stones have you had?

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What are some of the symptoms I could experience?

Patients with PH1 may experience different symptoms at different times in life; some will experience symptoms as babies, while others may not have symptoms until later in life. While symptoms vary from person to person, oxalate is always overproduced in the body and can cause damage to the kidneys and other organs.

Kidney stone symptoms can include:

Pain in the side of the body
Dysuria (painful urination)
Hematuria (blood in the urine)
Urinary tract infections (UTIs)

If you think you are experiencing these symptoms, consider contacting your doctor or a urologist.

These are not all the possible symptoms of a kidney stone.

Symptoms of end-stage kidney disease (ESKD) can include:

Producing little or no urine
Feeling ill and tired
Loss of appetite, nausea, and vomiting
Pale skin color
Swelling of the hands and feet
In PH1, decreased kidney function that can lead to oxalate depositing throughout the body

These are not all the possible symptoms of end-stage kidney disease.

If you think you are experiencing these symptoms, consider contacting your doctor or a nephrologist. By keeping track of your kidney health, you and your doctor can make more informed decisions.

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Can someone in my family have PH1, too?

PH1 is an autosomal recessive disease that is passed down within families. That's why it is important that family members, especially siblings, of a person with PH1 should consider getting tested for the disease.

PH1 can affect members of the same family in different ways, including how the disease presents itself and/or how it progresses.

If a healthcare provider suspects PH1, they may recommend a test to measure the amount of oxalate in the urine or blood, as a first step toward diagnosis.

Or a healthcare provider may recommend that family members be tested with a genetic test (a method doctors use to help confirm a PH1 diagnosis through a blood or saliva sample) to aid in determining if they have the disease. If you are an immediate family member of a person with PH1, speak with your doctor about whether genetic testing makes sense for you.

Your doctor is your best source of information if you ever have questions about your health.

SEE ONE OPTION FOR GENETIC TESTING

If you haven’t been diagnosed with PH1, you or your healthcare provider can request genetic testing and counseling through the Alnylam Act^® program offered at no charge, if you meet certain criteria. The test is done using a blood, saliva, or buccal sample. Siblings and family members may also be tested through Alnylam Act^®. The Alnylam Act^® program was created to provide access to genetic testing and counseling to patients as a way to help people make more informed decisions about their health.

While the program is sponsored by Alnylam Pharmaceuticals, all services are performed by independent third parties. For more information and program rules, download a brochure at AlnylamActPH1.com.

If you haven’t been diagnosed with PH1, you or your healthcare provider can request genetic testing and counseling through the Alnylam Act^® program offered at no charge, if you meet certain criteria. The test is done using a blood, saliva, or buccal sample. Siblings and family members may also be tested through Alnylam Act^®. The Alnylam Act^® program was created to provide access to genetic testing and counseling to patients as a way to help people make more informed decisions about their health.

While the program is sponsored by Alnylam Pharmaceuticals, all services are performed by independent third parties. For more information and program rules, download a brochure at AlnylamActPH1.com.

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