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. 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. In a healthy liver, oxalate is present only in small amounts. As oxalate is not used by the body, it is removed 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. In the Middle East and North Africa cases of PH1 are more common.

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 too much oxalate is produced by your liver and builds up in the kidneys. High levels of oxalate can damage the kidneys and affect your body's ability to filter waste from the blood. This can also damage organs, and can lead to kidney failure.

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PH1 Patient Perspectives: Describing PH1

Patients and Caregivers Describe Primary Hyperoxaluria Type 1
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PH1 causes the liver to make too much oxalate.

In PH1, oxalate is overproduced due to a broken process that involves the liver enzymes called glycolate oxidase (GO) and alanine: glyoxylate aminotransferase (AGT). Think of your liver as a factory, and these enzymes that work there as machines that help your body make or break down substances. Watch how this happens, below:

About Primary Hyperoxaluria Type 1 - Video 1

Because PH1 is caused by oxalate overproduction, your doctor will monitor the levels of oxalate within your body.

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. This substance is transformed by AGT into an amino acid for your body to use. Amino acids help to build proteins in the body.

Abnormal Process in Liver for Glycolate Oxidase and Alanine Glyoxylate Aminotransferase

In PH1, AGT is broken, but GO continues to work

GO continues to make the building block, but because of an error in your genes (called a gene mutation), AGT isn't working the way it should. As a result of this mutation, that building block gets made into oxalate instead. This results in too much oxalate being made (overproduction).

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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

In PH1, oxalate is constantly overproduced and can cause the disease to progress, meaning that it 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 urine. When oxalate and calcium combine, crystals are formed. Over time, more and more crystals are made that get trapped in the kidneys. These crystals can damage your kidneys and affect their ability to filter waste from your body in two ways:

Kidney Stones Illustration

Crystals can join together to create hard masses (kidney stones, or nephrolithiasis)

Nephrocalcinosis Illustration

Calcium oxalate can form and be deposited on the kidneys (called nephrocalcinosis)

People with PH1 can have both kidney stones and calcium crystals in the kidneys. With or without symptoms, oxalate continues to be overproduced and the damage caused by oxalate may get worse over time (called progression). PH1 can progress at different rates in different people, and the damage it causes 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 build-up of crystals in the kidneys can lead to chronic kidney disease (CKD) or even kidney failure, also known as end-stage renal disease (ESRD).

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

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

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 do not have stones.

PH1 may present in a number of ways:

Having kidney stones,
even only one, as a child

Having repeated kidney stones (recurrent kidney stones)

Finding crystals in kidney tissue during a kidney test (nephrocalcinosis)

Kidney failure (end-stage renal disease or ESRD)

Not growing sufficiently as a baby (failure to thrive)

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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.

Mum of an adult with PH1

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The signs of PH1 may not always be noticeable; they can go unrecognised or be confused with the signs of other disorders. Adults with PH1 can wait several years or longer after experiencing their first symptom before they receive a PH1 diagnosis. Because PH1 gets worse over time, it’s important that PH1 is diagnosed as early as possible, so that you can take proactive steps to manage your PH1.

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 professional. They can help you decide if you should speak to a kidney specialist (nephrologist).

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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What are some of the symptoms I could experience?

Kidney stone symptoms can include:

  • Pain in the back or sides of the body
  • Pain when you urinate
  • Blood in the urine (hematuria)
  • Urinary tract infections (UTIs)
  • Passing stones in urine

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, poor kidney function that can lead to oxalate spreading 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 about your care.

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Can someone in my family have PH1 too?

PH1 is an inherited condition, meaning that it is passed down within families. It is important that family members, especially siblings, of a person with PH1 consider getting tested for the disease via a genetic test.

Family members can find out if they have the disease by getting a genetic test using a blood or saliva sample.

PH1 can affect members of the same family in different ways, including how the disease presents itself and/or how it progresses. PH1 is an inherited condition, meaning that it is passed down within families. It is important that family members, especially siblings, of a person with PH1 consider getting tested for the disease via a genetic test.

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 Handbook

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

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What's next

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

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PH1-CEMEA-00003    April 2021

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