Kidney Week

Abstract: TH-PO0613

Potentially Treatable Steroid-Resistant Nephrotic Syndrome (SRNS) Diagnosed via Comprehensive Renal Genetic Testing

Session Information

• Monogenic Kidney Diseases: Glomerular
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases

Authors

• Raible, Darbey, Natera, Inc., Austin, Texas, United States

Darbey Raible, MS

• Huang, Dongmei, SUNY Upstate Medical University Hospital, Syracuse, New York, United States

Dongmei Huang, MD

• Harris, Jill M., Natera, Inc., Austin, Texas, United States

Jill M. Harris, MS

• Schurman, Scott, SUNY Upstate Medical University Hospital, Syracuse, New York, United States

Scott Schurman, MD

Introduction

Coenzyme Q10 (CoQ10) deficiency is a rare autosomal recessive disorder with a variable clinical spectrum ranging from isolated nephrotic syndrome to multisystem disease with prominent neurologic involvement. Early diagnosis is crucial, as some patients respond to oral CoQ10 supplementation. Moreover, identifying the underlying genetic etiology of nephrotic syndrome can prevent exposure to unnecessary immunosuppressive therapies. We present a case in which a comprehensive renal gene panel testing led to the diagnosis of CoQ10 deficiency in a child with steroid resistant nephrotic syndrome (SRNS).

Case Description

A 17-month-old male with developmental delay presented with generalized edema, profound proteinuria, and hypoalbuminemia. Renal function was preserved at presentation. He was diagnosed with nephrotic syndrome and started on corticosteroids. After four weeks, he remained unresponsive to treatment. A kidney biopsy revealed collapsing focal segmental glomerulosclerosis (FSGS) without global sclerosis. Simultaneously, genetic testing via a panel of 385 genes associated with inherited chronic kidney disease (the Renasight^TM test; Natera, Austin, TX) identified a likely pathogenic variant and a variant of uncertain significance (VUS) in the COQ2 gene. Parental studies revealed biparental inheritance, confirming these COQ2 variants to be in trans. The VUS was subsequently reclassified as a likely pathogenic variant, and a molecular diagnosis of autosomal recessive COQ2-related primary CoQ10 deficiency was confirmed. Immunosuppressive therapy was discontinued. Oral CoQ10 supplementation (30 mg/kg/day) was initiated two months after presentation. By this time, however, the patient had developed oliguria and had progressed to end-stage renal disease (ESRD). He remains peritoneal dialysis-dependent without meaningful recovery of residual renal function.

Discussion

Accurate and early molecular diagnosis using comprehensive renal genetic testing can uncover rare, potentially treatable forms of SRNS, enabling targeted therapy and avoiding unnecessary immunosuppression. Although CoQ10 supplementation did not halt disease progression in this case, earlier intervention might hold therapeutic potential in similarly affected patients.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025jq8t1nhb