Background Immunoglobulin A deficiency (IgAD) is the most common form of primary immunodeficiency in western countries. It can be associated with the development of autoimmune diseases both in adults and in children even though the exact pathophysiology is not fully defined. Case Presentation We report here a case of a young patient who developed nephrotic syndrome secondary to membranoproliferative glomerulonephritis associated with the incidental finding of IgAD. We began corticosteroid therapy and angiotensin-converting enzyme inhibitor, and we observed partial remission of the nephrotic syndrome after about nine months; nonetheless, in the following follow-up visits, a progressive decline of renal function was found. Conclusion Our case extends the spectrum of hitherto described glomerulonephritides associated with IgAD which were described until now.

Background: Congenital obstructive uropathy (COU) is a common cause of developmental defects of the urinary tract, with heterogeneous clinical presentation and outcome. Genetic analysis has the potential to elucidate the underlying diagnosis and help risk stratification. Methods: We performed a comprehensive genomic screen of 733 independent COU cases, which consisted of individuals with ureteropelvic junction obstruction (UPJO; n=321), ureterovesical junction obstruction/congenital megaureter (UVJO; n=178), and congenital hydronephrosis not otherwise specified (COU-NOS; n=234). We identified pathogenic single nucleotide variants (SNVs) in 53 (7.2%) cases and genomic disorders in 23 (3.1%) cases. No significant differences in the overall diagnostic yield among COU sub-phenotypes nor pathogenic SNVs in several genes were associated with any of the three categories. Discussion: Although COU may appear phenotypically heterogeneous, COU phenotypes are likely to share common molecular bases. However, mutations in TNXB were more often identified in COU-NOS cases, demonstrating the diagnostic challenge in discriminating COU from hydronephrosis secondary to vesicoureteral reflux, particularly when diagnostic imaging is incomplete. Pathogenic SNVs in only six genes were found in more than one individual, supporting high genetic heterogeneity. Finally, convergence between data on SNVs and genomic disorders suggest MYH11 as a dosage-sensitive gene possibly correlating with severity of COU. Conclusion: We established a genomic diagnosis in 10.0% of COU individuals. The findings underscore the urgent need to identify novel genetic susceptibility factors to COU to better define the natural history of the remaining 90% of cases without a molecular diagnosis.