Cyclosporine A responsive congenital nephrotic syndrome with single heterozygous variants in NPHS1, NPHS2, and PLCE1

  • Anna Eichinger
  • Sabine Ponsel
  • Carsten Bergmann
  • Roman Günthner
  • Julia Hoefele
  • Kerstin Amann
  • Bärbel Lange-Sperandio
Brief Report

Abstract

Background

Congenital nephrotic syndrome (CNS) is primarily a monogenetic disease, with the majority of cases due to changes in five different genes: the nephrin (NPHS1), podocin (NPHS2), Wilms tumor 1 (WT1), laminin ß2 (LAMB2), and phospholipase C epsilon 1 (PLCE1, NPHS3) gene. Usually CNS is not responsive to immunosuppressive therapy, but treatment with ACE inhibitors, AT1 receptor blockade and/or indomethacin can reduce proteinuria. If the disease progresses to end-stage renal disease, kidney transplantation is the therapy of choice.

Case-Diagnosis

Here, we present the case of a 4-month-old girl with congenital nephrotic syndrome. Upon admission, the patient presented with life-threatening anasarca, hypoalbuminemia, proteinuria, and impaired growth. There was no evidence of an infectious or immunological etiology. The genetic evaluation revealed a heterozygous variant in NPHS1 (p.Arg207Trp), in NPHS2 (p.Ser95Phe) as well as in PLCE1 (p.Ala1045Ser) and did not explain CNS. In addition to daily parenteral albumin infusions plus furosemide, a pharmacological antiproteinuric therapy was started to reduce protein excretion. Based on the genetic results, immunosuppressive therapy with prednisolone was initiated, but without response. However, following cyclosporine A treatment, the patient achieved complete remission and now has good renal function, growth, and development.

Conclusions

A profound search for the cause of CNS is necessary but has its limitations. The therapeutic strategy should be adapted when the etiology remains unclear.

Keywords

Congenital nephrotic syndrome Cyclosporine A NPHS1 NPHS2 PLCE1 

Notes

Acknowledgements

We thank the patient and her parents for participating in this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© IPNA 2018

Authors and Affiliations

  1. 1.Dr. v. Hauner Children’s Hospital, Division of Pediatric NephrologyLudwig-Maximilians UniversityMunichGermany
  2. 2.Center for Human GeneticsBioscientiaIngelheimGermany
  3. 3.Institute of Human GeneticsTechnical University of MunichMunichGermany
  4. 4.Department of NephrologyTechnical University of MunichMunichGermany
  5. 5.Institute for PathologyUniversity Hospital ErlangenErlangenGermany

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