ABOUT PRIMARY HYPEROXALURIA TYPE 1 (PH1):

It’s okay to have questions.

You may be overwhelmed to receive a diagnosis of primary hyperoxaluria type 1 (PH1) and want to know more about what it means to have this disease. The good news is you aren't alone. This is a resource for answers to common questions about PH1.

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What is PH1?

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

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 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 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 of PH1 is often kidney stones (nephrolithiasis/urolithiasis). Kidney stones form because oxalate is overproduced by your liver. High levels of oxalate can also lead to kidney failure and damage to other organs.

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PH1 Perspectives: Describing PH1

Patients and Caregivers Describe Primary Hyperoxaluria Type 1
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Why is oxalate overproduced in primary hyperoxaluria type 1 (PH1)?

In PH1, oxalate is overproduced due to a broken process that involves the liver enzymes glycolate oxidase (GO) and alanine:glyoxylate aminotransferase (AGT). Enzymes are molecules that help your body make or break down substances. Watch how this happens, below:

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.

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, this process is broken. GO continues to make that building block, but because of a gene mutation (change), AGT isn’t working the way it should. As a result, that building block gets made into oxalate instead.

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What can happen when oxalate is overproduced?

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.

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.

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:

Kidney Stones Illustration

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

Nephrocalcinosis Illustration

Crystals deposit in the kidneys themselves (called nephrocalcinosis)

People with PH1 can 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 renal disease (ESRD).

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.

Systemic Oxalosis Illustration
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What are the signs of PH1 to look for?

Although kidney stones are the most common, and often the first symptom 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 renal disease (kidney failure)

Failure to thrive
(not growing sufficiently as a baby)

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PH1 Perspectives: Journey to Diagnosis

Hear Parents Describe the Path to Their Children's Primary Hyperoxaluria Type 1 Diagnoses
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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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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 your healthcare provider. They can help you determine if you should consult with a nephrologist (kidney specialist).

Testing as early as possible with a urine and genetic test for PH1 may shorten the often long time it takes for people to get diagnosed.

 
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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 reasons to believe you could have 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?

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.

Symptoms of end-stage renal disease (ESRD) 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

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

Family members can be tested with a genetic test (a simple way to confirm a PH1 diagnosis through a blood or a saliva sample) to determine if they have the disease.

PH1 can affect members of the same family in different ways, including how the disease presents itself and/or how it progresses. Family members should ask their healthcare provider if they should consider getting genetically tested for PH1 even if they have no noticeable symptoms of the disease.

SEE ONE OPTION FOR GENETIC TESTING

If you haven’t been diagnosed with PH1, your healthcare provider can request genetic testing and counseling through the Alnylam Act® program if you meet certain criteria. The test is simple—it is done using a blood or a saliva sample. Siblings and family members may also be tested through Alnylam Act®.

If you haven’t been diagnosed with PH1, your healthcare provider can request genetic testing and counseling through the Alnylam Act® program if you meet certain criteria. The test is simple—it is done using a blood or a saliva sample. Siblings and family members may also be tested through Alnylam Act®.

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PH1 Perspectives: Experience with Genetic Testing

Video About Genetic Testing for Primary Hyperoxaluria Type 1
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PH1 Handbook

You can customize and download your own PH1 Handbook, which provides an overview of PH1 management, monitoring, and more.

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So
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So, what’s next?

Explore ways you and your care team can help you take on PH1.

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