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

NCT ID: NCT04885179

Last Updated: 2025-10-24

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 120 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-04-22
• Study Completion Date: 2028-12-30

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.

Detailed Description

This protocol aims to gather information about sphingosine phosphate lyase insufficiency syndrome (SPLIS), a condition also known as NPHS14 or familial steroid-resistant nephrotic syndrome with adrenal insufficiency. SPLIS is a recently discovered genetic disease caused by recessive mutations in the SGPL1 gene. SPLIS can have effects on the kidney, adrenal gland, brain, skin, and blood cells. Some patients with SPLIS do not survive beyond infancy, whereas others live to adulthood. By monitoring the natural history of SPLIS over time in affected patients, the investigators will establish a clinical baseline that reflects how the disease progresses over time. This information may be useful in future clinical trials. The results may reveal which types of SGPL1 mutations correlate with best and worst patient outcomes. Some SPLIS patients are current on a regimen of high dose vitamin B6 supplementation on the advice of their treating physician. By including patients treated with B6, our study may provide evidence for the impact of B6 treatment on biochemical and blood markers of the disease. Our overall goals are to characterize the clinical, biochemical and metabolic manifestations of SPLIS and how these manifestations change over time within individuals with this condition.

Conditions

Sphingolipidoses; Enzyme Deficiency

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Individuals with SPLIS

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

no intervention

Intervention Type: OTHER

No interventions are involved in this observational study.

Parents of individuals with SPLIS

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

no intervention

Intervention Type: OTHER

No interventions are involved in this observational study.

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.

no intervention

Intervention Type: OTHER

No interventions are involved in this observational study.

Interventions

no intervention

No interventions are involved in this observational study.

Intervention Type: OTHER

Eligibility Criteria

Exclusion Criteria

• prisoners
• pregnant women
• healthy volunteers with:

• diabetes,
• infection,
• fever,
• known HIV/AIDS,
• cardiac disease
• or anemia.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Julie D Saba, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California San Francisco

San Francisco, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Julie D Saba, MD, PhD

Role: CONTACT

Julie.Saba@ucsf.edu

510-414-6317

Joanna Y Lee, PhD

Role: CONTACT

Joanna.Lee@ucsf.edu

510-590-8292

Facility Contacts

Julie D Saba, MD, PhD

Role: primary

Julie.Saba@ucsf.edu

510-414-6317

Joanna Y Lee, PhD

Role: backup

Joanna.Lee@ucsf.edu

510-590-8292

References

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Reference Type: BACKGROUND

PMID: 28165339 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28165343 (View on PubMed)

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, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK562988/

Reference Type: BACKGROUND

PMID: 33074640 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30274713 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32233035 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32855188 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33755599 (View on PubMed)

Other Identifiers

20-32291

Identifier Type: -

Identifier Source: org_study_id