An Overview of PH1

Primary hyperoxaluria type 1 (PH1) is a progressive genetic disease which is potentially life-threatening, and often presents with kidney stones.1-3

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What is PH1?

Primary hyperoxaluria (PH) is a group of autosomal-recessive diseases resulting from defects in different enzymes involved in glyoxylate metabolism that lead to an overproduction of oxalate in the liver.2,3

There are 3 types of PH: PH1, PH2, and PH3, each of which is caused by a defect in a different enzyme.3 PH1 often presents with kidney stones and is caused by a defect in the liver-specific enzyme alanine:glyoxylate aminotransferase (AGT).1,3 Normally, AGT processes glyoxylate, which is generated by another liver enzyme, glycolate oxidase (GO).2,3

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PH1 is the most common—and most severe—type of PH1,3,4

70%-80% of PH cases are PH1. Even so, PH1 is a rare disease, affecting an estimated 1 to 3 people in one million in Europe and the United States, and higher prevalence in the Middle East and North Africa region.1,3-5

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PH1 can result in irreparable kidney damage1,3

One of the most devastating aspects of PH1 is that it causes a progressive decline in kidney function, typically culminating in end-stage renal disease (ESRD).1,3,6 Moreover, there is the potential risk of systemic oxalosis.3

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Early diagnosis is key to mitigating damage2,3,6-8

Disease‐mitigating strategies can lessen damage by reducing stone formation and renal deposition of calcium oxalate crystals; this underscores the importance of early diagnosis and intervention.3,8 Unfortunately, ~50% of PH1 patients may be undiagnosed, although data on prevalence are limited.9

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PH1 is progressive and typically systemic2,10

See how PH1 can be life-threatening2

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PH1 typically leads to progressive decline in renal function.2

Liver oxalate overproduction may lead to inflammation and progressive kidney function decline following calcium oxalate crystal formation.10 Continuous oxalate overproduction may lead to irreversible damage in the kidneys and other organs.10

PH1 advances at variable rates, typically progressing to ESRD.2 When the kidneys are unable to excrete oxalate effectively due to toxicity from calcium oxalate crystal deposition, systemic oxalosis—the widespread tissue deposition of calcium oxalate—can occur.10 Complications from systemic oxalosis can be fatal.2

In some instances, renal function can decline after a single incident of dehydration due to acute illness or intense physical activity.11-15 This can occur even in patients with previously stable disease.12

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What causes oxalate overproduction in PH1?

Inability of AGT to process glyoxylate made by GO2

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PH1 is a genetic disease caused by mutations in the AGXT gene that renders the liver enzyme AGT dysfunctional.3

Normally, AGT processes glyoxylate, which is generated by another liver enzyme, GO.2,3 In PH1, a defect in AGT means glyoxylate is instead converted to oxalate.2 Oxalate cannot be metabolized and is typically excreted by the kidneys at normal levels.3 When overproduced as it is in PH1, oxalate can wreak progressive, irreversible damage.2 Oxalate combines with calcium, creating calcium oxalate crystals.2 These crystals attach to renal tissues, where they can aggregate to form kidney stones or lead to nephrocalcinosis.2,10 As calcium oxalate accumulates, renal excretion is impaired, and crystals deposit throughout the body.10

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Kim Hollander - Oxalosis and Hyperoxaluria Foundation

"Given the nature of this disease, PH1 can go undiagnosed for many years. Early symptoms in adults, such as kidney stones, are often attributed to other, much more common conditions. We need to help physicians recognize symptoms faster, to stop progression before a patient reaches end-stage renal failure."

Kim Hollander

Executive Director, Oxalosis and Hyperoxaluria Foundation

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