Primary hyperoxaluria type 1 (PH1) is a severe autosomal recessive inherited disorder
of glyoxylate metabolism caused by mutations in the AGXT gene on chromosome 2q37.3
that encodes the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase. These
mutations are found throughout the entire gene and cause a wide spectrum of clinical
severity. Rare in Europe, PH1 is responsible for 13% of the end stage renal failure
in the Tunisian child. In the present work, we identified the double mutation c.32C>T
(Pro11Leu) and c.731T>C (p.Ile244Thr) in AGXT gene in five unrelated Tunisian families
with PH1 disease. Our results provide evidence regarding the potential involvement
of c.32C>T, originally described as common polymorphism, on the resulting phenotype.
We also reported an extreme intrafamilial heterogeneity in clinical presentation of
PH1. Despite the same genetic background, the outcome of the affected members differs
widely. The significant phenotypic heterogeneity observed within a same family, with
a same genotype, suggests the existence of relevant modifier factors.