A Rare NPHS2 Mutation (E130K) in Hereditary Steroid‐Resistant Nephrotic Syndrome: A Case Report

TL;DR

A rare NPHS2 gene mutation (E130K) was found in a child with steroid-resistant nephrotic syndrome, highlighting the need for genetic testing and early diagnosis.

Contribution

Reports a novel E130K NPHS2 mutation in a case of hereditary steroid-resistant nephrotic syndrome with atypical clinical features.

Findings

Compound heterozygous NPHS2 mutations (R138X and E130K) were identified in a child with steroid-resistant nephrotic syndrome.

Renal biopsy showed minimal change disease with negative immunofluorescence, supporting the genetic diagnosis.

Early genetic testing and renal biopsy are critical for diagnosing rare cases of steroid-resistant nephrotic syndrome.

Abstract

Hereditary steroid‐resistant nephrotic syndrome (HSRNS) due to mutations in the NPHS2 gene (encoding podocin) is a rare genetic condition that typically presents in childhood. We report a case of a 2‐year‐and‐8‐month‐old male, the seventh child of consanguineous parents, who presented with recurrent fever, febrile tonic‐clonic seizures, and periorbital edema. His medical history included multiple hospitalizations in infancy due to suspected sepsis and chest infections. Upon admission, laboratory findings revealed proteinuria, hypoalbuminemia, and hypercholesterolemia, along with mild hepatomegaly. Genetic testing identified compound heterozygous mutations (R138X and E130K) in the NPHS2 gene, confirming a diagnosis of HSRNS. Renal biopsy revealed features consistent with minimal change disease, and immunofluorescence was negative for IgG, IgM, IgA, C3, and C4. The patient was treated with enalapril as part of supportive management. This case highlights the importance of early genetic testing and renal biopsy in diagnosing steroid‐resistant nephrotic syndrome, particularly in children with atypical presentations. Understanding the genetic underpinnings of such rare cases is essential for guiding appropriate treatment and providing prognostic insights.