Abstract: FR-PO0143
Pyridoxine Therapy for Nephrotic Syndrome Due to Sphingosine Phosphate Lyase Insufficiency Syndrome
Session Information
- Hereditary Glomerular and Tubulointerstitial Kidney Diseases
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Nelson-Taylor, Sarah K., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Blanchette, Eliza, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
Introduction
Congenital nephrotic syndrome (NS), is a form of steroid-resistant NS, that is resistant to immunosuppression and can progress to ESKD in early childhood. Pathogenic variants in NPHS1, NPHS2, WT1 and LAMB2 account for >85% of cases, however >50 genes have been implicated. Co-enzyme Q10 supplementation in patients with NS due to primary CoQ10 deficiency is the only established gene-specific therapy. Here, we present a patient with NS due to sphingosine phosphate lyase insufficiency syndrome (SPLIS) who was able to achieve disease remission with pyridoxine supplementation.
Case Description
A 15 mo female with developmental delay and 6 months of poor weight gain was admitted with respiratory failure and septic shock due to pneumonia. Evaluation was notable for hypoalbuminemia, nephrotic range proteinuria, and diffuse anasarca consistent with a clinical diagnosis of NS. A renal biopsy was obtained which showed diffuse podocyte foot process effacement without significant glomerular pathology. Whole genome sequencing identified a homozygous pathogenic variant in SGPL1 (c1247A>G, pTyr416Cys). Pyridoxine supplementation was started on day 4 of admission, with subsequent resolution of clinical nephrotic syndrome prior to discharge on day 23. Pyridoxine supplementation was continued, with sustained remission of NS and stable stage 2 CKD (GFR 72 mL/min/1.73m2) at 2 year follow up.
Discussion
SPLIS is an inborn error of sphingolipid metabolism that results from inactivating mutations in the gene SGPL1 which encodes the enzyme sphingosine phosphate lyase (SPL). SPLIS is a multisystem disorder characterized by childhood onset steroid-resistant NS which progresses to ESKD. SPL is a pyridoxal-5 phosphate (PLP)-dependent enzyme and supplementation with the PLP precurosor pyridoxine can restore enzymatic activity in some SGPL1 variants. Pyridoxine supplementation in this case resulted in a sustained remission of the patient’s NS without further CKD progression. This case highlights the importance of broad genetic testing in patients with congenital and steroid-resistant forms of NS and provides evidence to support empiric use of pyridoxine supplementation in patients with SPLIS.