Five Month-Old With Renal Failure and Hematuria
H&E stain, 100X
H&E stain and polarized light, 50X
Transmission electron microscopy image
Renal Biopsy Diagnosis: Primary Hyperoxaluria
Oxalosis occurs when the kidneys do not eliminate sufficient calcium oxalate crystals from the body through the urine. Because the kidneys stop functioning, oxalate crystals are deposited elsewhere in the body such as the eyes and other major organs.
Primary hyperoxaluria is a rare condition that is usually caused by a defective gene in liver and other cells. There are three types of primary hyperoxaluria: I, II and III. Types I and II are both autosomal recessive disorders caused by liver and other cell enzyme deficiencies but type II is milder and does not usually cause end-stage renal disease. Type III is poorly defined with an unknown cause. Type I primary hyperoxaluria is estimated to occur in 1 per 60,000 to 120,000 live births; it is more common in some Mediterranean countries, such as Tunisia. The incidence of type II primary hyperoxaluria is unknown; it is less common than type 1.
Primary hyperoxaluria is characterized by the overproduction of a substance called oxalate (or oxalic acid). In the kidneys, the excess oxalate combines with calcium to form calcium oxalate, a hard compound that is the main component of kidney stones. Deposits of calcium oxalate can lead to kidney damage, kidney failure, and injury to other organs. Sugar and amino acid metabolism produces glyoxylate that is normally converted to the amino acid glycine or to a compound called glycolate through the action of alanine-glyoxylate aminotransferase (AGXT gene) and glyoxylate reductase/hydroxypyruvate reductase (GRHPR gene), respectively. Mutations in the AGXT (type I disease) or GRHPR (type II disease) gene cause a shortage of these enzymes, which prevents the conversion of glyoxylate to glycine or glycolate. As levels of glyoxylate build up, it is converted to oxalate instead. Oxalate combines with calcium to form calcium oxalate, which is what causes the severe kidney and other organ damage.
The diagnosis of hyperoxaluria is made by measuring the oxalic acid level in the urine of affected people and a specific diagnosis is obtained from enzyme analysis of a liver biopsy. A prenatal diagnosis may require fetal liver biopsy. It is difficult to predict the severity of hyperoxaluria that is related to supersaturation of urine oxalate and calcium. Combined liver and kidney transplantation is the current definitive therapy for patients with severe disease.
Online information: www.ohf.org/about_ph.html
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4. Millan MT, Berquist WE, et al: One hundred percent patient and kidney allograft survival with simultaneous liver and kidney transplantation in infants with primary hyperoxaluria: a single-center experience. Transplantation. 2003 Nov 27;76(10):1458-63.