Primary Hyperoxaluria Type 1: A Cause for Infantile Renal Failure and Massive Nephrocalcinosis

Abstract

Primary hyperoxaluria type 1 is a rare autosomal-recessive disease caused by the deficient activity of the liver specific enzyme alanine-glyoxylate aminotransferase. Increased endogenous oxalate production induces severe hyperoxaluria, recurrent urolithiasis, progressive nephrocalcinosis and renal failure. Here we report a 6 month old boy who presented with vomiting and decreased urine volume. He was diagnosed with chronic kidney failure at 4 months of age and peritoneal dialysis was introduced at a local hospital. His parents were third degree cousins and family history revealed 2 maternal cousins who developed end stage renal disease during childhood. When he was admitted to our hospital, laboratory studies were consistent with end stage renal disease, ultrasound showed bilateral massive nephrocalcinosis. As clinical presentation was suggestive for primary hyperoxaluria type 1, plasma oxalate was determined and found extremely elevated. Genetic testing proved diagnosis by showing a disease causing homozygous mutation (AGXT-gene: c.971_972delT). The patient was put on pyridoxine treatment and aggressive dialysis programme. In conclusion; progressive renal failure in infancy with massive nephrocalcinosis, especially if accompanied by consanguinity and family history, should always raise the suspicion of PH type 1. Increased awareness of the disease would help physicians in both treating the patients and guiding the families who have diseased children and plan to have further pregnancies.

Oxalate retinopathy is irreversible despite early combined liver-kidney transplantation in primary hyperoxaluria type 1

“…The most severe form of hyperoxaluria is type 1 (PH1), caused by a defect of the peroxisomal liver enzyme alanine glyoxylate aminotransferase (AGT) . Some patients develop end‐stage renal disease (ESRD) already in the first months or years of life (infantile oxalosis [IO]) . These children are at great risk of extrarenal complications such as cardiomyopathy, pathologic bone fractures, and especially retinal oxalate deposition, which leads to severe visual impairment .…”

Primary hyperoxaluria type 1 – two case reports

“…It may present at any age and clinical manifestations range from infantile massive nephrocalcinosis and failure to thrive to recurrent or only occasional stone formation. 1,2,5 Recurrent urolithiasis and/or progressive nephrocalcinosis are most often the first symptoms and, particularly if there is a suggestive family history or consanguinity, these should raise the suspicion of PH1 and motivate a metabolic screening. 1,5 Some patients Inês Ganhão, Catarina Borges, Marta Amorim, Marisa Braga da Cruz, Susana Nobre, Telma Francisco, Dinorah Cardoso, Margarida Abranches…”

“…2 ESRD is present at diagnosis in more than 50% of the patients. 1,5 Studies demonstrate an average of 5 years from the first symptoms to the definitive diagnosis that may be attributed to the heterogeneous presentation and limited knowledge of the disease among medical community. 5 In both cases discussed above, one and a half years passed between initial symptoms and suspicion of diagnosis and another one and a half years until definitive diagnosis.…”

“…Oxalate is poorly soluble and forms calcium oxalate crystals, leading to recurrent urolithiasis and/or nephrocalcinosis, culminating in renal failure. 1,2,5,6 Over 50% already present with end stage renal disease (ESRD) at time of diagnosis. 1 Progressive decline in estimated glomerular filtration rate (eGFR) results in reduced oxalate excretion by the kidneys, while the liver continues to product excess of oxalate, leading to increased plasma oxalate levels (oxalosis) and systemic oxalate deposition in several organs.…”

“…1 Progressive decline in estimated glomerular filtration rate (eGFR) results in reduced oxalate excretion by the kidneys, while the liver continues to product excess of oxalate, leading to increased plasma oxalate levels (oxalosis) and systemic oxalate deposition in several organs. 2,5,6 CASE REPORTS…”