Background: Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS) is a rare metabolic disorder caused by SGPL1 mutations, leading to dysfunction of sphingosine-1-phosphate lyase, an enzyme essential for sphingolipid metabolism. SPLIS is characterized by steroid-resistant nephrotic syndrome and lymphocyte depletion. For patients progressing to end-stage kidney disease(ESKD), kidney transplantation necessitates careful immunosuppression management to balance rejection risk with infection risk. However, guidance on the optimal immunosuppression regimen for SPLIS patients remains limited. Here, we describe our approach for a pediatric patient with ESKD secondary to SRNS due to SPLIS who underwent deceased donor kidney transplantation.
Case Presentation: This is a case of a boy who was diagnosed with nephrotic syndrome at age two. Despite >3 months of high-dose prednisolone, he remained steroid-resistant. Kidney biopsy revealed focal segmental sclerosis, negative immunofluorescence, and no deposits on electron microscopy. His renal function declined rapidly, requiring dialysis within a year. Whole-exome sequencing perfomed a few years later identified SGPL1 variants of uncertain significance: [c.1186C>T(p.Arg396Trp)] and [c.1247A>G(p.Tyr416Cys)]. These, along with phenotypic characteristics—including adrenal insufficiency, hypothyroidism, bilateral hearing loss, and ichthyosis—suggested SPLIS. At age nine, he underwent deceased donor kidney transplantation from a 23-year-old donor with KDPI of 4% and a six-antigen mismatch. CMV D+/R+, EBV D+/R-. Pre-transplant evaluation showed low CD19(49 cells/μL) and CD3(280 cells/μL) counts and 0% PRA. Given the six-antigen mismatch, thymoglobulin induction would typically be used. However, due to lymphocyte depletion, induction therapy was modified to basiliximab, administered on post-transplant day(POD) 0 and POD 4, alongside intravenous methylprednisolone. Maintenance therapy consisted of tacrolimus, mycophenolate, and prednisone. Tacrolimus trough levels goal: month 1: 8-10 ng/mL, month 2: 6-8 ng/mL, and 5-7 ng/mL thereafter. Donor-derived cell-free DNA remained between 0.2-0.3%, with no donor-specific antibodies detected. CD19 and CD3 counts persisted low. Routine viral monitoring, including CMV, EBV, and BK PCR, remained negative. At six-months post-transplant, the patient had stable renal function(creatinine: 0.45 mg/dL). 
Conclusion: This case highlights the feasibility of kidney transplantation in SPLIS, a rare metabolic disorder characterized by SRNS and lymphocyte depletion. Our immunosuppressive strategy—basiliximab induction with tacrolimus, mycophenolate, and prednisone maintenance—achieved stable graft function while minimizing infections despite persistently low lymphocyte counts. This case provides valuable insight into SPLIS immunosuppression management, suggesting that a similarly tailored approach may benefit patients with immune dysregulation.