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

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.

• Authors: Anna Eichinger, Sabine Ponsel, Carsten Bergmann, Roman Günthner, Julia Hoefele, Kerstin Amann, Bärbel Lange-Sperandio
• Journal: Pediatric nephrology (Berlin, Germany) (Pediatr Nephrol) Vol. 33 Issue 7 Pg. 1269-1272 (07 2018) ISSN: 1432-198X [Electronic] Germany
• PMID: 29663071 (Publication Type: Case Reports, Journal Article)

Chemical References

• Immunosuppressive Agents
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• NPHS2 protein
• nephrin
• Cyclosporine
• Phosphoinositide Phospholipase C
• phospholipase C epsilon

Topics

• Cyclosporine (therapeutic use)
• Drug Therapy, Combination (methods)
• Female
• Genetic Testing
• Heterozygote
• Humans
• Immunosuppressive Agents (therapeutic use)
• Infant
• Intracellular Signaling Peptides and Proteins (genetics)
• Kidney (diagnostic imaging, pathology)
• Membrane Proteins (genetics)
• Nephrotic Syndrome (congenital, diagnosis, drug therapy, genetics)
• Phosphoinositide Phospholipase C (genetics)
• Polymorphism, Single Nucleotide
• Proteinuria (congenital, diagnosis, drug therapy, genetics)
• Treatment Outcome
• Ultrasonography