Primary Hyperoxaluria

Claire, living with PH1

PRIMARY HYPEROXALURIA

Understanding Primary Hyperoxaluria Type 1

Primary hyperoxaluria (PH) constitutes a group of rare inherited disorders of the liver characterized by the overproduction of oxalate, an end-product of metabolism. High levels of oxalate are toxic because oxalate cannot be broken down by the human body and accumulates in the kidneys.

There are 3 types of PH: type 1 (PH1), type 2 (PH2), and type 3 (PH3). PH1 is the most common and the most severe form, accounting for 70% to 80% of all cases. PH1 is an ultra-rare, inherited disease in which excessive amounts of oxalate are produced by the liver. PH1 affects 1 to 3 individuals per million, with a higher prevalence in some regions, such as the Middle East and North Africa. In the United States and Europe, there may be approximately 2,500 to 5,000 cases. Currently, the only definitive treatment for PH1 is a liver transplant. If the patient has already progressed to kidney failure, then a dual liver/kidney transplant is required.

What are the Symptoms of PH1?

People with PH1 often experience the formation of oxalate stones throughout the urinary tract and kidneys.
When a person with PH1 has a kidney stone, symptoms can include:

 Flank pain  Urinary tract infections  Painful urination  Blood in the urine

Some individuals are not diagnosed until after their kidneys have failed and they require dialysis to help filter waste products from the blood.

PH1 Inside the Body

Disease onset
& progression

Patients can be diagnosed with PH1 at any age, but most individuals experience their first symptoms in early childhood.

For many patients, PH1 is not diagnosed immediately. Since kidney stones in adults are more commonplace, adult patients with PH1 often spend many years undiagnosed until they present with severe kidney disease.

PH1 Manifestations by Stage of Life

As PH1 progresses, it often results in end-stage renal disease, a life-threatening condition that prevents the kidneys from filtering fluids and waste from the body effectively.

Consequently, the build-up of oxalate can lead to the deposition of oxalate crystals in the eyes, bones, skin, heart, and central nervous system, causing diminished vision, bone fractures, ulcers, heart failure, and other complications.

CLINICAL TRIALS

Interested in learning about our primary hyperoxaluria studies? Get started here.

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PATIENT ADVOCACY

At Alnylam, we put you at the center of everything we do. We have a team dedicated to collaborating with patient advocacy groups and individuals affected by these rare diseases.

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References

  1. Edvardsson VO, Goldfarb DS, Lieske JC, et al. Hereditary causes of kidney stones and chronic kidney disease. Peadiatr Nephrol. 2013;28:1923-1942.
  2. Hopp K, Cogal A, Bergstralh E, et al. Phenotype-genotype correlations and estimated carrier frequencies of primary hyperoxaluria. J Am Soc Nephrol. 2015;26:2559-2570.
  3. Milliner DS, Harris PC, Cogal AG, Lieske JC. Primary hyperoxaluria type 1. GeneReviews, University of Washington, Seattle. 1993-2018.
  4. Lorenz EC, Michet CJ, Milliner DS, Lieske JC. Update on oxalate crystal disease. Curr Rheumatol Rep. 2013;7:340.
  5. Zhao F, Bergstralh EJ, Mehta RA, et al. Predictors of incident ESRD among patients with primary hyperoxaluria presenting prior to kidney failure. Clin J Am Soc Nephrol. 2016;11:119-126.
  6. Hoppe B, Beck BB, Milliner DS. The primary hyperoxalurias. Kidney Int. 2009;75:1264-1271.
  7. Cochat P, Deloraine A, Rotily M, Olive F, Liponski I, Deries N. Epidemiology of primary hyperoxaluria type 1. Nephrol Dial Transplant. 1885;10(Suppl 8):3-7.
  8. Cochat P, Rumsby G. Primary hyperoxaluria. N Engl J Med. 2013,369:649-658.
  9. Harambat J, Fargue S, Acquaviva C, et al. Genotype–phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome. Kidney Int. 2010;77:443–449.

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