Primary Hyperoxaluria

Abstract

Primary hyperoxalurias (PH) are inborn errors in the metabolism of glyoxylate and oxalate. PH type 1, the most common form, is an autosomal recessive disorder caused by a deficiency of the liver-specific enzyme alanine, glyoxylate aminotransferase (AGT) resulting in overproduction and excessive urinary excretion of oxalate. Recurrent urolithiasis and nephrocalcinosis are the hallmarks of the disease. As glomerular filtration rate decreases due to progressive renal damage, oxalate accumulates leading to systemic oxalosis. Diagnosis is often delayed and is based on clinical and sonographic findings, urinary oxalate assessment, DNA analysis, and, if necessary, direct AGT activity measurement in liver biopsy tissue. Early initiation of conservative treatment, including high fluid intake, inhibitors of calcium oxalate crystallization, and pyridoxine in responsive cases, can help to maintain renal function in compliant subjects. In end-stage renal disease patients, the best outcomes have been achieved with combined liver-kidney transplantation which corrects the enzyme defect.

Massive bone marrow involvement in an end stage renal failure case with erythropoietin-resistant anemia and primary hyperoxaluria

“…There are three subtypes depending on the hereditary enzyme deficiencies, type 1 (PH1), type 2 (PH2) and type 3 (PH3). 8 PH1 is characterized by the lack of the AGT enzyme which normally would detoxify the glyoxylate found in hepatic peroxisomes. Due to the lack of this enzyme peroxisomal glyoxylate turns into oxalate and due to the poor solubility of calcium oxalate, crystallization occurs primarily in the kidneys and other organs.…”

“…Consequently, liver damage, reduction in glomerular filtration rate, ESRD and systemic oxalosis develops. 8 Oxalosis is the final stage of the hyperoxaluric syndrome. Different diagnostic and therapeutic approaches are available for this condition in both developed and developing countries.…”

“…9 Apart from the medical treatment the ideal course of action would be to plan organ transplantation prior to the development of ESRD and systemic oxalosis. 8 Isolated kidney or combined kidney-liver transplantations are implemented for the treatment of primary hyperoxaluria however; transplantation strategies need to be developed in order to protect the kidney from oxalate damage. 16 The transplantation options given to PH1 cases include isolated kidney, isolated liver and combined kidney and liver transplantations.…”

“…5 Retinal deposition of oxalate can be easily recognized and can be the first symptom of systemic oxalosis. 5,8 Other fundamental oxalate deposition areas are medias of arteries, peripheric nervous system (neuropathy), myocardia (AV block), thyroid and skin (livedo reticularis). 5 This report presents the case of a patient with chronic renal failure and oxalosis diagnosed with massive bone marrow involvement who underwent a bone marrow biopsy due to the erythropoietin (EPO) resistant anaemia.…”

Hyperoxalurie primaire de type 1 : de l’enfance à l’âge adulte, comment gérer adéquatement l’adhésion au traitement médical ?

“…Le dé ficit de cette enzyme, dont le cofacteur est la pyridoxine, entraîne une surproduction hé patique d'acide oxalique, composé é liminé par le rein. Vu les concentrations é levé es, l'oxalate urinaire se lie au calcium pour former des cristaux, lits des lithiases d'oxalate calcique [1].…”