Abstract: PUB307
Apparent Steroid Sensitivity in Congenital Nephrotic Syndrome Type 1 (NPHS1)
Session Information
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Al-Awad, Mohammad Salim Lutfi /M.S, Hamad Medical Corporation, Doha, Ad Dawhah, Qatar
- Abuhelaiqa, Essa, Hamad Medical Corporation, Doha, Ad Dawhah, Qatar
- Nauman, Awais, Hamad Medical Corporation, Doha, Ad Dawhah, Qatar
Introduction
Congenital Nephrotic Syndrome (CNS) Type1 is an autosomal recessive disease caused by mutation in NPHS1 gene. NPHS1 encodes for Nephrin which is essential for maintaining slit diaphragm integrity. Herein we report a case of CNS Type1 that was treated with multiple Immunosuppressants with numerous relapses and remission giving an apparent impression of steroid sensitivity
Case Description
A 21 y.o male, diagnosed with Nephrotic Syndrome at age of 20 months, Received Steroids initially with partial response. Later, The patient continued to exhibit low grade proteinuria less than 1 g/24hr with sharp interval increases reminiscent of relapses. Despite treatment with Cyclophosphamide, Mycophenolate Mofetil and Cyclosporin, his relapses persisted
Kidney Biopsy at age of 10 years when he was in partial remission revealed no Glomerular Proliferative changes or Segmental Sclerosing lesions with minimal IFTA, Negative IF. EM Showed moderate and non-global foot process effacement and was decided to have Minimal Change Disease in partial remission. He was maintained on Cyclosporine and Prednisone and continued to have frequent relapses. Therefore, he was given Rituximab, other therapies were tapered off as there was partial improvement of proteinuria. The patient had preserved GFR through all clinical course. and noted that the patient had fluctuation of proteinuria with no particular relationship with Immunosuppression therapy which led to the suspicion of CNS type1. He was referred to Genetic Testing which revealed NPHS1-related disorder with Homozygous mutation of (TTC>GTC): c.2617 T>G in exon 19 of the NPHS1 gene
Discussion
CNS type1 (NPHS1) Classically is characterized by prenatal onset of massive proteinuria followed by severe steroid-resistant nephrotic syndrome apparent at birth with rapid progression to end-stage renal failure. When NPHS1 patients are on therapy partial improvement in proteinuria can give an apparent impression of steroid sensitivity resulting in continued use of various immunosuppressive which are potentially toxic. Genetic testing can confirm the diagnosis thereby avoiding pernicious side effects of immunosuppression. Our patient had relapsing-remitting Nephrotic syndrome with no relation to therapy. It is therefore imperative to maintain high index of suspicion and low threshold for considering genetic testing in childhood Nephrotic Syndrome