Case Report: CMV-Associated Congenital Nephrotic Syndrome

Anju Jacob

Shameer Habeeb

Leal Herlitz

Eva Simkova

Click here for additional data file.^{(18K, DOCX)}

^{Department of Pediatrics, Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates}

^{Kidney Centre of Excellence, Al Jalila Children's Speciality Hospital, Dubai, United Arab Emirates}

^{Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, United States}

^{Al Jalila Genomics Center, Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates}

^{Section of Infectious Diseases, Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates}

^{Department of Genetics, Mohammad Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates}

Edited by: Sami Sanjad, American University of Beirut Medical Center, Lebanon

Reviewed by: Mario Giordano, Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari, Italy; Vera Maria Santoro Belangero, Campinas State University, Brazil

*Correspondence: Martin Bitzan ea.hcja@naztib.nitram

This article was submitted to Pediatric Nephrology, a section of the journal Frontiers in Pediatrics

Edited by: Sami Sanjad, American University of Beirut Medical Center, Lebanon

Reviewed by: Mario Giordano, Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari, Italy; Vera Maria Santoro Belangero, Campinas State University, Brazil

Received 2020 Jul 4; Accepted 2020 Nov 2.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

Background: Congenital nephrotic syndrome, historically defined by the onset of large proteinuria during the first 3 months of life, is a rare clinical disorder, generally with poor outcome. It is caused by pathogenic variants in genes associated with this syndrome or by fetal infections disrupting podocyte and/or glomerular basement membrane integrity. Here we describe an infant with congenital CMV infection and nephrotic syndrome that failed to respond to targeted antiviral therapy. Case and literature survey highlight the importance of the “tetrad” of clinical, virologic, histologic, and genetic workup to better understand the pathogenesis of CMV-associated congenital and infantile nephrotic syndromes.

Case Presentation: A male infant was referred at 9 weeks of life with progressive abdominal distention, scrotal edema, and vomiting. Pregnancy was complicated by oligohydramnios and pre-maturity (34 weeks). He was found to have nephrotic syndrome and anemia, normal platelet and white blood cell count, no splenomegaly, and no syndromic features. Diagnostic workup revealed active CMV infection (positive CMV IgM/PCR in plasma) and decreased C3 and C4. Maternal anti-CMV IgG was positive, IgM negative. Kidney biopsy demonstrated focal mesangial proliferative and sclerosing glomerulonephritis with few fibrocellular crescents, interstitial T- and B-lymphocyte infiltrates, and fibrosis/tubular atrophy. Immunofluorescence was negative. Electron microscopy showed diffuse podocyte effacement, but no cytomegalic inclusions or endothelial tubuloreticular arrays. After 4 weeks of treatment with valganciclovir, plasma and urine CMV PCR were negative, without improvement of the proteinuria. Unfortunately, the patient succumbed to fulminant pneumococcal infection at 7 months of age. Whole exome sequencing and targeted gene analysis identified a novel homozygous, pathogenic variant (2071+1G>T) in NPHS1.

Literature Review and Discussion: The role of CMV infection in isolated congenital nephrotic syndrome and the corresponding pathological changes are still debated. A search of the literature identified only three previous reports of infants with congenital nephrotic syndrome and evidence of CMV infection, who also underwent kidney biopsy and genetic studies.

Conclusion: Complete workup of congenital infections associated with nephrotic syndrome is warranted for a better understanding of their pathogenesis (“diagnostic triad” of viral, biopsy, and genetic studies). Molecular testing is essential for acute and long-term prognosis and treatment plan.

Keywords: Finnish-type nephrotic syndrome, NPHS1, cytomegalovirus, Streptococcus pneumoniae, case report, glomerulonephritis, infantile nephrotic syndrome

Abstract

Acknowledgments

We thanked Dr. Muhammad Anwar for his help with the kidney biopsy and all physicians, nurses, and allied health professionals who contributed to the care and well-being of the described patient and his family.

Acknowledgments

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