primary hyperoxaluria type 1

What Is Primary Hyperoxaluria Type 1?

Primary Hyperoxaluria Type 1 (PH1) is an inherited disease caused by mutations in the AGXT gene in which the deficiency of a particular liver enzyme causes the body to accumulate excess amounts of a substance called oxalate. Excess oxalate leads to a buildup of insoluble calcium salts in the kidneys and other organs, resulting in progressive organ damage. Accumulation of calcium oxalate in the kidneys may cause kidney stones and progressive kidney failure. Deposits in the urinary tract can lead to difficulty with urination, blood in the urine, and recurrent urinary tract infections. Insoluble calcium deposits in other body tissues can lead to bone pain; vision loss; tingling, numbness, or pain in the extremities; enlargement of the liver and spleen; and problems with the electrical system of the heart (heart block).

The majority of affected individuals develop symptoms of the condition between birth and the age of 25, although later onset is possible. In roughly 20% of affected individuals, symptoms of PH1 develop by six months of age. Patients with this severe form often develop early end-stage kidney disease, occasionally within the first year of life. More than half of individuals with PH1 have disease onset in childhood or adolescence. In those with onset in adolescence, the most common presentation is kidney stones. In contrast, those who present earlier in childhood commonly experience difficulty with urination, blood in the urine, and have recurrent urinary tract infections. Some affected individuals do not show symptoms until their forties or fifties.

How Common Is Primary Hyperoxaluria Type 1?

The overall prevalence of PH1 ranges from 1 in 1,000,000 to 3 in 1,000,000 individuals. It may be more common in Tunisia, Iran, and Israeli Arab and Druze populations.

How Is Primary Hyperoxaluria Type 1 Treated?

Treatments for PH1 are mainly aimed at preventing the formation and deposition of calcium oxalate. Increased fluid intake is extremely important. Calcium-oxalate crystallization inhibitors (i.e., potassium or sodium citrate, orthophosphate, and magnesium) and dietary interventions may be recommended. Supplementation with vitamin B6 (pyridoxine) is effective in approximately 30% of patients.

Early liver transplantation or transplantation of both the liver and kidneys is an option. Because a deficient liver enzyme leads to kidney failure, early liver transplantation may avoid the need for a kidney transplant. Kidney transplantation alone is not sufficient, as the affected liver could destroy the new kidneys as well.

Individuals with PH1 should avoid extremely large doses of vitamin C as well as foods high in oxalate, including chocolate, rhubarb, and starfruit.

What Is the Prognosis for an Individual with Primary Hyperoxaluria Type 1?

The prognosis for an individual with PH1 is variable and depends on how early the disease is detected and treated. Without treatment, PH1 leads to progressive kidney failure and eventually death. For most patients, end-stage kidney disease occurs in the third to the fifth decade. However, approximately 80% of patients with onset in infancy will be diagnosed with end-stage kidney disease by the age of 3. For those with onset in childhood, 50% will develop end-stage kidney disease by the age of 15. Death in the first decade of life is possible for those with early-onset disease.

Following organ transplant, some individuals with PH1 have lived normal or near-normal lifespans.