Clinical and genetic characteristics of Japanese nephronophthisis patients.

Background: Nephronophthisis (NPH) accounts for 4-5 % of end-stage renal disease occurring in childhood.

Method: We investigated the clinical context and characteristics of renal and extrarenal symptoms, as well as the NPHP genes, in 35 Japanese patients with clinical and histologic features suggesting NPH.

Results: NPH occurred fairly uniformly throughout Japan irrespective of region or gender. In three families, NPH affected siblings. The median age of patients was 12.5 years. Renal abnormalities attributable to NPH discovered through mass screening, such as urine tests in school. However, NPH accounted for less than 50 % of children with abnormal findings, including incidentally discovered renal dysfunction during evaluation of extrarenal symptoms or during routine check-ups. Typical extrarenal manifestations leaded to discovery including anemia and delayed physical development. The urine often showed low gravity specific density and low molecular weight proteinuria. Frequent renal histologic findings included cystic dilation of tubules, mainly in the medulla, and irregularity of tubular basement membranes. Genetically abnormalities of NPHP1 were not common, with large deletions frequently noted. Compound heterozygotes showing single abnormalities in each of NPHP1, NPHP3, and NPHP4 were observed.

Conclusions: Our findings resemble those reported in Western populations.