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Wilms' tumor suppressor gene (WT1) en codes a tran scription factor required for nor mal development of the genitourinary system. Germline WT1 mutations have been described in a wide spectrum of pathological conditions, including kidney diseases, genital abnormalities and Wilms' tumor. Here we re port a 4-year-old male patient who presented with bilateral cryptorchidism, Wilms' tumor, nephroblastomatosis and renal failure with out nephrotic proteinuria. Sequence analysis of the WT1 gene demonstrated a constitutional heterozygous non sense mutation in exon 7, which leads to a truncation of the WT1 protein at the zinc-finger 1. In the DNA of the tumor, we ob served the same mutation in homo/hemizygosity. Given the requirement of WT1 for nor mal development, the WT1 mutation is likely to be responsible for the nephroblastomatosis and, in con sequence, for the severe renal failure ob served in our patient. This finding ex tends the spectrum of kidney diseases related to WT1 mutations and points to the need to screen for this gene in children with genitourinary abnormalities and Wilms' tumor be cause of the associated risk of nephroblastomatosis and renal failure in those carrying WT1 mutations.

Fabry disease is an X-linked recessive inborn error of glycosphingolipid metabolism caused by the deficient activity of the lysosomal enzyme, alpha-galactosidase A. Enzyme replacement therapy (ERT) for this disorder has been available in Europe since 2001. However, its effect on advanced renal failure remains controversial. We report the case of a patient whose decline in renal function was reduced by the administration of ERT (agalsidase-alpha). This reduction was more pronounced after doubling the dose of the enzyme. The rate of deterioration of eGFR went from 6.3 ml/min/year prior to the start of ERT (0.2 mg/kg) to 2 ml/min/year (0.4 mg/kg). To our knowledge, this is the first reported case of a patient with moderately impaired renal function treated with high doses of ERT and follow-up of 6 years. The data shown here suggest that ERT may have a very positive impact on renal function even in advanced stages. The role of proteinuria and its control seem to have a clear responsibility for this favorable outcome.