SPL Insufficiency Syndrome (SPLIS)/NPHS14: a SPLIS Observational Study and Patient Registry (International)

NCT04885179 | Recruiting

• 1 other identifier: 20-32291
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This protocol aims to gather information about sphingosine phosphate lyase insufficiency syndrome (SPLIS), also known as NPHS14, and to create a SPLIS patient registry. Medical records, radiological and pathology results, blood test results, and genetic information will be collected. Samples of blood, cheek cells, urine and stool may be collected for analysis. If a skin biopsy has been performed for medical care, cells from the biopsy may be analyzed. No treatment or other intervention is involved in this study. However, the effect of treatments administered by the patient's physician may be detected and monitored based on changes in the blood or urine.

Conditions

Sphingolipidoses; Enzyme Deficiency

Keywords

SPLIS; sphingosine phosphate lyase; SGPL1; sphingolipidosis; steroid-resistant nephrotic syndrome; primary adrenal insufficiency; neurological defect

Outcome Measures

Primary Outcomes (1)

• Survival

  The primary outcome of this study is survival (age at death).

  0-99 years

Secondary Outcomes (1)

• Onset of nephrotic syndrome

  0-99 years

Other Outcomes (4)

• Onset of primary adrenal insufficiency

  0-99 years

• Responsiveness of blood sphingolipid levels to vitamin B6 supplementation

  0-99 years

• Skin fibroblast sphingolipid levels in response to vitamin B6

  1-6 weeks

Study Arms (3)

Individuals with SPLIS

Individuals diagnosed with SPLIS based on genetic testing that confirms bi-allelic pathogenic variants in SGPL1

Other: no intervention

Parents of individuals with SPLIS

Parents of individuals diagnosed with SPLIS based on genetic testing that confirms bi-allelic pathogenic variants in SGPL1

Other: no intervention

age and gender-matched controls

The investigators will attempt to collect biological specimens from individuals closely matched to SPLIS patient cohort by age and gender. This group may include siblings, cousins, and unrelated healthy children and adults.

Other: no intervention

Interventions

no intervention OTHER

No interventions are involved in this observational study.

Individuals with SPLIS; Parents of individuals with SPLIS; age and gender-matched controls

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

SPLIS is a genetic disorder caused by recessive mutations in SGPL1. The study population includes individuals with confirmed bi-allelic mutations in SGPL1, regardless of age, gender, disease manifestations, or treatments received. Some patients with SPLIS will have kidney failure, adrenal insufficiency and/or neurological problems. Parents, family members and unrelated healthy individuals enrolled during routine health appointments, elective surgical procedures and other medical interactions will be included as healthy controls.

You may not qualify if:

• prisoners
• pregnant women
• healthy volunteers with:
• diabetes,
• infection,
• fever,
• known HIV/AIDS,
• cardiac disease
• or anemia.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California San Francisco

San Francisco, California, 94143, United States

RECRUITING

Related Publications (7)

• Lovric S, Goncalves S, Gee HY, Oskouian B, Srinivas H, Choi WI, Shril S, Ashraf S, Tan W, Rao J, Airik M, Schapiro D, Braun DA, Sadowski CE, Widmeier E, Jobst-Schwan T, Schmidt JM, Girik V, Capitani G, Suh JH, Lachaussee N, Arrondel C, Patat J, Gribouval O, Furlano M, Boyer O, Schmitt A, Vuiblet V, Hashmi S, Wilcken R, Bernier FP, Innes AM, Parboosingh JS, Lamont RE, Midgley JP, Wright N, Majewski J, Zenker M, Schaefer F, Kuss N, Greil J, Giese T, Schwarz K, Catheline V, Schanze D, Franke I, Sznajer Y, Truant AS, Adams B, Desir J, Biemann R, Pei Y, Ars E, Lloberas N, Madrid A, Dharnidharka VR, Connolly AM, Willing MC, Cooper MA, Lifton RP, Simons M, Riezman H, Antignac C, Saba JD, Hildebrandt F. Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency. J Clin Invest. 2017 Mar 1;127(3):912-928. doi: 10.1172/JCI89626. Epub 2017 Feb 6.

  PMID: 28165339 BACKGROUND

• Prasad R, Hadjidemetriou I, Maharaj A, Meimaridou E, Buonocore F, Saleem M, Hurcombe J, Bierzynska A, Barbagelata E, Bergada I, Cassinelli H, Das U, Krone R, Hacihamdioglu B, Sari E, Yesilkaya E, Storr HL, Clemente M, Fernandez-Cancio M, Camats N, Ram N, Achermann JC, Van Veldhoven PP, Guasti L, Braslavsky D, Guran T, Metherell LA. Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome. J Clin Invest. 2017 Mar 1;127(3):942-953. doi: 10.1172/JCI90171. Epub 2017 Feb 6.

  PMID: 28165343 BACKGROUND

• Weaver KN, Sullivan B, Hildebrandt F, Strober J, Cooper M, Prasad R, Saba J. Sphingosine Phosphate Lyase Insufficiency Syndrome. 2020 Oct 15. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK562988/

  PMID: 33074640 BACKGROUND

• Choi YJ, Saba JD. Sphingosine phosphate lyase insufficiency syndrome (SPLIS): A novel inborn error of sphingolipid metabolism. Adv Biol Regul. 2019 Jan;71:128-140. doi: 10.1016/j.jbior.2018.09.004. Epub 2018 Sep 25.

  PMID: 30274713 BACKGROUND

• Zhao P, Liu ID, Hodgin JB, Benke PI, Selva J, Torta F, Wenk MR, Endrizzi JA, West O, Ou W, Tang E, Goh DL, Tay SK, Yap HK, Loh A, Weaver N, Sullivan B, Larson A, Cooper MA, Alhasan K, Alangari AA, Salim S, Gumus E, Chen K, Zenker M, Hildebrandt F, Saba JD. Responsiveness of sphingosine phosphate lyase insufficiency syndrome to vitamin B6 cofactor supplementation. J Inherit Metab Dis. 2020 Sep;43(5):1131-1142. doi: 10.1002/jimd.12238. Epub 2020 May 4.

  PMID: 32233035 BACKGROUND

• Martin KW, Weaver N, Alhasan K, Gumus E, Sullivan BR, Zenker M, Hildebrandt F, Saba JD. MRI Spectrum of Brain Involvement in Sphingosine-1-Phosphate Lyase Insufficiency Syndrome. AJNR Am J Neuroradiol. 2020 Oct;41(10):1943-1948. doi: 10.3174/ajnr.A6746. Epub 2020 Aug 27.

  PMID: 32855188 BACKGROUND

• Zhao P, Tassew GB, Lee JY, Oskouian B, Munoz DP, Hodgin JB, Watson GL, Tang F, Wang JY, Luo J, Yang Y, King S, Krauss RM, Keller N, Saba JD. Efficacy of AAV9-mediated SGPL1 gene transfer in a mouse model of S1P lyase insufficiency syndrome. JCI Insight. 2021 Apr 22;6(8):e145936. doi: 10.1172/jci.insight.145936.

  PMID: 33755599 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Leftover skin biopsy material or fibroblasts derived from skin biopsies obtained as part of medical care may be used to create a cell line that will be analyzed and stored in a SPLIS specimen bank at UCSF.

MeSH Terms

Conditions

Sphingolipidoses; Nephrotic Syndrome; Addison Disease

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders; Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Julie D Saba, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julie D Saba, MD, PhD

CONTACT

510-414-6317; Julie.Saba@ucsf.edu

Joanna Y Lee, PhD

CONTACT

510-590-8292; Joanna.Lee@ucsf.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Target Duration: 10 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: May 13, 2021
• Study Start: April 22, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2028
• Last Updated: October 24, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)