Update on primary hyperoxaluria in Italian patients

10^th European Nephrology Conference

October 24-26, 2016 Rome, Italy

Alessandra Pelle

University of Torino, Italy
SSD Genetica Medica, Italy
AOU San Luigi Gonzaga, Italy

Posters & Accepted Abstracts: J Nephrol Ther

Abstract :

Primary hyperoxalurias (PH) are a group of rare autosomal recessive diseases commonly arising in childhood and presenting with nephrolithiasis, nephrocalcinosis, progressing to chronic renal failure. 3 responsible genes are known: Alanine-glyoxylate aminotransferase (AGXT, PH1), glyoxylate reductase/hydroxypyruvate reductase (GRHPR, PH2) and 4-hydroxy-2-oxoglutarate aldolase (HOGA1, PH3). Out of over 200 patients from all Italy referred until April 2016 to the multidisciplinary network established in Torino in the 80s, PH1 had been diagnosed in 82, PH2 in 3, PH3 in 2 DZ twins and one additional patient homozygous for a novel HOGA1 variant of unknown significance (c.341-81delT). A defined suspicion of PH strictly depends on a reliable dosage of urinary oxalate that it is strongly influenced by the analytical procedure (free vs. bound Uox), in particular in the advanced phase of the disease. This may in part explain why PH is underdiagnosed. 21 patients suspected to have PH on clinical grounds were negative for mutations in the 3 genes. Negative findings might be ascribed in a few cases to mutations of difficult identification by Sanger sequencing. Alternatively, new genetic subtypes of PH can also be hypothesized, caused by mutations in other genes encoding proteins of glyoxylate metabolism (e.g. HAO1, SLC26A1). To explore this possibility, whole exome sequencing and SNPs array techniques and further phenotype�genotype studies are needed. This approach requires a closer interaction between clinicians and geneticists in evaluating the clinical and biochemical data: A multiple step diagnostic algorithm based on clinical and biochemical data could be proposed to achieve this goal.

Biography :

Email: alessandraelisapelle@gmail.com