Case Report: CMV-Associated Congenital Nephrotic Syndrome
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...
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| Format: | Article |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2020.580178/full |
| _version_ | 1818875521959723008 |
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| author | Anju Jacob Shameer M. Habeeb Shameer M. Habeeb Leal Herlitz Eva Simkova Eva Simkova Jwan F. Shekhy Alan Taylor Alan Taylor Walid Abuhammour Walid Abuhammour Ahmad Abou Tayoun Ahmad Abou Tayoun Ahmad Abou Tayoun Martin Bitzan Martin Bitzan |
| author_facet | Anju Jacob Shameer M. Habeeb Shameer M. Habeeb Leal Herlitz Eva Simkova Eva Simkova Jwan F. Shekhy Alan Taylor Alan Taylor Walid Abuhammour Walid Abuhammour Ahmad Abou Tayoun Ahmad Abou Tayoun Ahmad Abou Tayoun Martin Bitzan Martin Bitzan |
| author_sort | Anju Jacob |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T13:27:50Z |
| format | Article |
| id | doaj.art-b0a1794ad07a4ca8b5608927b2cac373 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-12-19T13:27:50Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-b0a1794ad07a4ca8b5608927b2cac3732022-12-21T20:19:30ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602020-11-01810.3389/fped.2020.580178580178Case Report: CMV-Associated Congenital Nephrotic SyndromeAnju Jacob0Shameer M. Habeeb1Shameer M. Habeeb2Leal Herlitz3Eva Simkova4Eva Simkova5Jwan F. Shekhy6Alan Taylor7Alan Taylor8Walid Abuhammour9Walid Abuhammour10Ahmad Abou Tayoun11Ahmad Abou Tayoun12Ahmad Abou Tayoun13Martin Bitzan14Martin Bitzan15Department of Pediatrics, Al Jalila Children's Specialty Hospital, Dubai, United Arab EmiratesDepartment of Pediatrics, Al Jalila Children's Specialty Hospital, Dubai, United Arab EmiratesKidney Centre of Excellence, Al Jalila Children's Speciality Hospital, Dubai, United Arab EmiratesDepartment of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, United StatesDepartment of Pediatrics, Al Jalila Children's Specialty Hospital, Dubai, United Arab EmiratesKidney Centre of Excellence, Al Jalila Children's Speciality Hospital, Dubai, United Arab EmiratesDepartment of Pediatrics, Al Jalila Children's Specialty Hospital, Dubai, United Arab EmiratesDepartment of Pediatrics, Al Jalila Children's Specialty Hospital, Dubai, United Arab EmiratesAl Jalila Genomics Center, Al Jalila Children's Specialty Hospital, Dubai, United Arab EmiratesDepartment of Pediatrics, Al Jalila Children's Specialty Hospital, Dubai, United Arab EmiratesSection of Infectious Diseases, Al Jalila Children's Specialty Hospital, Dubai, United Arab EmiratesDepartment of Pediatrics, Al Jalila Children's Specialty Hospital, Dubai, United Arab EmiratesAl Jalila Genomics Center, Al Jalila Children's Specialty Hospital, Dubai, United Arab EmiratesDepartment of Genetics, Mohammad Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab EmiratesDepartment of Pediatrics, Al Jalila Children's Specialty Hospital, Dubai, United Arab EmiratesKidney Centre of Excellence, Al Jalila Children's Speciality Hospital, Dubai, United Arab EmiratesBackground: 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.https://www.frontiersin.org/articles/10.3389/fped.2020.580178/fullFinnish-type nephrotic syndromeNPHS1cytomegalovirusStreptococcus pneumoniaecase reportglomerulonephritis |
| spellingShingle | Anju Jacob Shameer M. Habeeb Shameer M. Habeeb Leal Herlitz Eva Simkova Eva Simkova Jwan F. Shekhy Alan Taylor Alan Taylor Walid Abuhammour Walid Abuhammour Ahmad Abou Tayoun Ahmad Abou Tayoun Ahmad Abou Tayoun Martin Bitzan Martin Bitzan Case Report: CMV-Associated Congenital Nephrotic Syndrome Frontiers in Pediatrics Finnish-type nephrotic syndrome NPHS1 cytomegalovirus Streptococcus pneumoniae case report glomerulonephritis |
| title | Case Report: CMV-Associated Congenital Nephrotic Syndrome |
| title_full | Case Report: CMV-Associated Congenital Nephrotic Syndrome |
| title_fullStr | Case Report: CMV-Associated Congenital Nephrotic Syndrome |
| title_full_unstemmed | Case Report: CMV-Associated Congenital Nephrotic Syndrome |
| title_short | Case Report: CMV-Associated Congenital Nephrotic Syndrome |
| title_sort | case report cmv associated congenital nephrotic syndrome |
| topic | Finnish-type nephrotic syndrome NPHS1 cytomegalovirus Streptococcus pneumoniae case report glomerulonephritis |
| url | https://www.frontiersin.org/articles/10.3389/fped.2020.580178/full |
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