Extreme intrafamilial variability of Saudi brothers with primary hyperoxaluria type 1

reme intrafamilial variability of Saudi brothers with primary hyperoxaluria type 1 Case report (958) Total Article Views Authors: Alfadhel M, Alhasan KA, Alotaibi M, Al Fakeeh K Published Date August 2012 Volume 2012:8 Pages 373 - 376 DOI: http://dx.doi.org/10.2147/TCRM.S34954 Received: 12 June 2012 Accepted: 24 July 2012 Published: 28 August 2012 Majid Alfadhel,1 Khalid A Alhasan,2 Mohammed Alotaibi,3 Khalid Al Fakeeh4 1Division of Genetics, Department of Pediatrics, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia; 2Division of Nephrology Department of Pediatrics, King Saud University King Khalid University Hospital, Riyadh, Saudi Arabia; 3Department of Radiology, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia; 4Division of Nephrology, Department of Pediatrics, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia Background: Primary hyperoxaluria type 1 (PH1) is characterized by progressive renal insufficiency culminating in end-stage renal disease, and a wide range of clinical features related to systemic oxalosis in different organs. It is caused by autosomal recessive deficiency of alanine:glyoxylate aminotransferase due to a defect in AGXT gene. Case report: Two brothers (one 6 months old; the other 2 years old) presented with acute renal failure and urinary tract infection respectively. PH1 was confirmed by high urinary oxalate level, demonstration of oxalate crystals in bone biopsy, and pathogenic homozygous known AGXT gene mutation. Despite the same genetic background, same sex, and shared environment, the outcome of the two siblings differs widely. While one of them died earlier with end-stage renal disease and multiorgan failure caused by systemic oxalosis, the older brother is pyridoxine responsive with normal development and renal function. Conclusion: Clinicians should be aware of extreme intrafamilial variability of PH1 and international registries are needed to characterize the genotype-phenotype correlation in such disorder.