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.

Key words

AGXT gene - consanguinity - end stage renal disease - hyperoxaluria - nephrocalcinosis

Schlüsselwörter

AGXT Gen - Blutsverwandtschaft - terminale Niereninsuffizienz - Hyperoxalurie - Nephrokalzinose

• References

• 1 Cibrik DM, Kaplan B, Arndorfer JA et. al. Renal allograft survival in patients with oxalosis. Transplantation 2002; 74: 707-710
• 2 Cochat P, Deloraine A, Rotily M et al. Epidemiology of primary hyperoxaluria type 1. Nephrol Dial Transplant 1995; 10 (Suppl. 08) 3-7
• 3 Cochat P, Liutkus A, Fargue S et al. Primary hyperoxaluria type 1: still challenging. Pediatr Nephrol 2006; 21: 1075-1081
• 4 Danpure CJ. Molecular aetiology of primary hyperoxaluria type 1. Nephron Exp Nephrol 2004; 98: 39-44
• 5 Diallo O, Janssens F, Hall M et al. Type 1 primary hyperoxaluria in pediatric patients: renal sonographic patterns. AJR 2004; 183: 1767-1770
• 6 Ellis SR, Hulton SA, McKiernan PJ et al. Combined liver–kidney transplantation for primary hyperoxaluria in young children. Nephrol Dial Transplant 2001; 16: 348-354
• 7 Hoppe B. An update on primary hyperoxaluria. Nat Rev Nephrol 2012; 8: 467-475
• 8 Milliner DS, Wilson DM, Smith LH. Clinical expression and long-term outcomes of primary hyperoxaluria types 1 and 2. J Nephrol 1998; 11 (Suppl. 01) 56-59
• 9 Monico CG, Rossetti S, Olson JB et al. Pyridoxine effect in type I primary hyperoxaluria is associated with the most common mutant allele. Kidney Int 2005; 67: 1704-1709
• 10 Monico CG, Rossetti S, Belostotsky R et al. Primary hyperoxaluria type III gene HOGA1 (formerly DHDPSL) as a possible risk factor for idiopathic calcium oxalate urolithiasis. Clin J Am Soc Nephrol 2011; 6: 2289-2295
• 11 Rumsby G, Williams E, Coulter-Mackie M. Evaluation of mutation screening as a first line test for the diagnosis of the primary hyperoxalurias. Kidney Int 2004; 66: 959-963
• 12 van Woerden CS, Groothoff JW, Wijburg FA et al. Clinical implications of mutation analysis in primary hyperoxaluria type 1. Kidney Int 2004; 66: 746-752