Is Cytomegalovirus a Partaker or a By-stander in Congenital Nephrotic Syndrome? : A novel mutation update.

Abstract

Congenital nephrotic syndrome (CNS) is a rare and serious disease of infants, which is due to a genetic and or an infectious cause. First case is an 11-week old baby, a completely worked-up case which includes the tetrad of clinical manifestations (neurological, gastro-intestinal and renal), virological findings (positive CMV antibody and DNA PCR), histo-pathological findings and novel genetic mutation (c.712+1G>C) in NPHS 1 gene. On the contrary, the second case is an 8-week old baby with isolated renal involvement of CMV infection. CMV IgM was positive but CMV DNA polymerase chain reaction (PCR) was negative. Parents were unwilling to do a genetic work up. In the first case partial remission of renal symptoms were achieved with Ganciclovir in four weeks, but she succumbed due to sepsis after being followed up for 730 days. The pediatrician of the second child skipped Ganciclovir and gave four weeks steroid trial. Due to absence of remission, renal biopsy was done and Tacrolimus was started. No recurrence of proteinuria was observed during the 14-month follow-up period. The need of anti-CMV therapy in isolated renal involvement of congenital CMV infection is questionable as the insult to the kidney has already occurred. It also highlights the dilemma perceived by a pediatrician, in starting anti-CMV therapy when CMV IgM antibodies are positive but CMV DNA PCR result is negative. This paper emphasizes the importance of performing a genetic test in every case of CNS to rule out any hereditary causes. Background Nephrotic syndrome presenting within first three months of life is defined as congenital nephrotic syndrome (CNS). It can be caused by genetic defects in structural proteins that form the glomerular filtration barrier or secondary to infections like congenital syphilis, toxoplasmosis and cytomegalovirus infection (CMV) which disrupt the podocytes and/or the basement membrane.1 Till 2020, only four completely worked up CMV IgM positive CNS cases were reported globally signifying the low incidence of detection.2 We present the case of two infants with congenital CMV infection and nephrotic syndrome, one of whom one received anti-CMV therapy while the other did not, and both of them experienced proteinuria remission.