ArticleJournal of inherited metabolic disease2020
Responsiveness of sphingosine phosphate lyase insufficiency syndrome to vitamin B6 cofactor supplementation.
Article in Journal of inherited metabolic disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Sphingosine Phosphate Lyase Insufficiency Syndrome - Observational Study and Patient Registry (International)
Natural History and Phenotypic Spectrum of Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS)
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Sphingosine phosphate lyase insufficiency syndrome: a systematic review.World journal of pediatrics : WJP · 2023Pooled it
- Association of vitamin B1/B6/B12 supplementation with sphingosine-1-phosphate signaling and its receptors in multiple sclerosis patients: relevance to LISPR1 and APOA1-AS.Bioscience reports · 2026Observational
- Redirection of sphingolipid metabolism drives cytoskeletal defects in SPLIS and reveals ROCK inhibition as therapy.The Journal of clinical investigation · 2026Article
- Higher Plasma Sphingosine-1-Phosphate Levels in Type 2 Diabetic Patients Have a Non-Linear Relationship with the Disease Prognostic Indices and Microvascular Complications: A Cross-Sectional Saudi Study.Journal of clinical medicine · 2026Article
- Human microbiota influence the immune cell composition and gene expression in the tumor environment of a murine model of glioma.Gut microbes · 2025Article
- Clinical presentation and management challenges of sphingosine-1-phosphate lyase insufficiency syndrome associated with an SGPL1 variant: a case report.BMC pediatrics · 2025Article
- Sphingosine phosphate lyase insufficiency syndrome as a primary immunodeficiency state.Advances in biological regulation · 2024Review
- Factors influencing survival in sphingosine phosphate lyase insufficiency syndrome: a retrospective cross-sectional natural history study of 76 patients.Orphanet journal of rare diseases · 2024Article
- [Research progress on monogenic inherited glomerular diseases with central nervous system symptoms].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024Review
- Prevalence estimate of sphingosine phosphate lyase insufficiency syndrome in worldwide and select populations.Genetics in medicine open · 2024Article
- Cronobacter sakazakii Pyridoxal Kinase PdxY Mediated by TreR and pESA3 Is Essential for Vitamin BApplied and environmental microbiology · 2023Article
- The Role of Microbiota-Derived Vitamins in Immune Homeostasis and Enhancing Cancer Immunotherapy.Cancers · 2023Review
- Combined novel homozygous variants in bothFrontiers in immunology · 2023Review
- Congenital adrenal calcifications as the first clinical indication of sphingosine lyase insufficiency syndrome: A case report and review of the literature.American journal of medical genetics. Part A · 2022Review
- A retrospective analysis of endocrine disease in sphingosine-1-phosphate lyase insufficiency: case series and literature review.Endocrine connections · 2022Review
- Insights From Long-term Follow-up of a Girl With Adrenal Insufficiency and Sphingosine-1-Phosphate Lyase Deficiency.Journal of the Endocrine Society · 2022Article
- Infantile nephrotic syndrome, immunodeficiency and adrenal insufficiency-a rare cause: Answers.Pediatric nephrology (Berlin, Germany) · 2022Article
- Neurological Consequences of Sphingosine Phosphate Lyase Insufficiency.Frontiers in cellular neuroscience · 2022Review
- The nutritional functions of dietary sphingomyelin and its applications in food.Frontiers in nutrition · 2022Review
- Efficacy of AAV9-mediated SGPL1 gene transfer in a mouse model of S1P lyase insufficiency syndrome.JCI insight · 2021Article
Corrections and comments
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Authors and funding
27 authors at 12 institutions in 5 countries.
Funding
Abstract
Sphingosine-1-phosphate (S1P) lyase is a vitamin B6-dependent enzyme that degrades sphingosine-1-phosphate in the final step of sphingolipid metabolism. In 2017, a new inherited disorder was described caused by mutations in SGPL1, which encodes sphingosine phosphate lyase (SPL). This condition is referred to as SPL insufficiency syndrome (SPLIS) or alternatively as nephrotic syndrome type 14 (NPHS14). Patients with SPLIS exhibit lymphopenia, nephrosis, adrenal insufficiency, and/or neurological defects. No targeted therapy for SPLIS has been reported. Vitamin B6 supplementation has therapeutic activity in some genetic diseases involving B6-dependent enzymes, a finding ascribed largely to the vitamin's chaperone function. We investigated whether B6 supplementation might have activity in SPLIS patients. We retrospectively monitored responses of disease biomarkers in patients supplemented with B6 and measured SPL activity and sphingolipids in B6-treated patient-derived fibroblasts. In two patients, disease biomarkers responded to B6 supplementation. S1P abundance and activity levels increased and sphingolipids decreased in response to B6. One responsive patient is homozygous for an SPL R222Q variant present in almost 30% of SPLIS patients. Molecular modeling suggests the variant distorts the dimer interface which could be overcome by cofactor supplementation. We demonstrate the first potential targeted therapy for SPLIS and suggest that 30% of SPLIS patients might respond to cofactor supplementation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.