Extreme intrafamilial variability of Saudi brothers with primary hyperoxaluria type 1

Abstract

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.

Keywords: PH1; intrafamilial variability; oxalosis; primary hyperoxaluria.

Figure 1

Sagittal ultrasound of the right kidney revealing presence of multiple crescent-shaped hyperechoic foci involving the renal pyramids consistent with renal medullary nephrocalcinosis.

Figure 2

Radiological findings in patient 2. Notes: (A) Ultrasound of the right kidney obtained in sagittal view demonstrates diffuse echogenicity involving the renal parenchyma. (B) Coronal reconstructed unenhanced computed tomography scan of the abdomen showed diffuse increased attenuation of both kidneys with more medullary increased density as compared to the renal cortex consistent with advanced nephrocalcinosis.