Recruiting

Observational Study

Sponsor:

UCLA

Code:

NCT06669949

Conditions

Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS)

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Interventions

no intervention

Study Details

Brief summary:

This is a prospective longitudinal natural history study with a retrospective cross-sectional arm aimed at determining the natural history of sphingosine phosphate lyase insufficiency syndrome (SPLIS), a recently recognized inborn error of metabolism. The central hypothesis is that age of onset, other disease features, and disease biomarkers will be predictive of quality of life (QOL) and survival in SPLIS patients.

Conditions

Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS)

Study ID

NCT06669949

Start date

Apr 22, 2025

Status verified date

Jul, 2026

Completion date

Dec 31, 2030

Anticipated

Primary completion date

Dec 31, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

All identified patients with SPLIS diagnosed by genetic criteria are eligible for enrollment in this study, regardless of baseline demographic, biochemical or metabolic features and regardless of interventions such as vitamin B6 supplementation, dialysis or kidney transplantation at time of enrollment. This study may include siblings of index SPLIS cases if the sibling has been genetically confirmed to have SPLIS, regardless of whether they have active disease at the time of enrollment. Data from deceased SPLIS patients will also be collected.

Inclusion Criteria:

Potential subjects fulfilling the following criteria will be eligible to participate in this study:

1. Living or deceased patients diagnosed with SPLIS based on

1. harbor biallelic pathogenic variant (PV) or likely PV (LPV) in the SGPL1 gene, regardless of phenotype OR
2. harbor nucleotide changes in both SGPL1 alleles, regardless of variant classification, if they also have one of the following: b1) exhibit at least 1 phenotypic feature of SPLIS (nephrosis, endocrine defect, ichthyosis, neuropathy, male gonadal dysgenesis, lymphopenia) b2) have evidence from biochemical or molecular data (such as enzyme expression or activity in skin fibroblasts) that indicate a possible loss of function in the S1P lyase (SPL) protein b3) are a sibling of a subject with nucleotide changes in both alleles of SGPL1 and at least 1 phenotypic feature of SPLIS
2. Informed consent and (if appropriate) assent for living subjects. For deceased subjects, the Principal Investigator (PI) will be responsible for ensuring that all requirements have been met in regard to the relevant local laws and regulations. Parents of participating SPLIS patients may be included as controls.

Exclusion Criteria:

Subjects with SPLIS (or their parents) who are currently using or have a history of using an investigational agent in the last 30 days with the exception of off-label use of medications will be excluded from the study

Study Design

Enrollment

28 participants

Anticipated

Interventions and Outcome Measures

Arms

Individuals with sphingosine phosphate lyase insufficiency syndrome

Individuals diagnosed with sphingosine phosphate lyase insufficiency syndrome based on genetic testing that confirms bi-allelic pathogenic variants in the SGPL1 gene

Parents of individuals with sphingosine phosphate lyase insufficiency syndrome

Parents of individuals diagnosed with sphingosine phosphate lyase insufficiency syndrome based on genetic testing that confirms bi-allelic pathogenic variants in the SGPL1 gene

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.

Interventions

no intervention

No interventions are involved in this observational study.

Primary outcome measure

  • Survival [ Time Frame: 3 years ]
  • Height [ Time Frame: 3 years ]
  • Weight [ Time Frame: 3 years ]
  • Head circumference [ Time Frame: 3 years ]
  • Triceps skin fold measurement [ Time Frame: 3 years ]
  • Subscapular skin fold measurement [ Time Frame: 3 years ]
  • Upper arm muscle circumference [ Time Frame: 3 years ]
  • Sitting height [ Time Frame: 3 years ]
  • Knee height [ Time Frame: 3 years ]
  • Tibial length [ Time Frame: 3 years ]
  • Nutritional intake assessment [ Time Frame: 3 years ]
  • Retinal condition [ Time Frame: 3 years ]
  • Skin condition [ Time Frame: 3 years ]
  • Charcot Marie Tooth Neuropathy Score (CMTNS) [ Time Frame: 3 years ]
  • Abdominal ultrasound [ Time Frame: At baseline ]
  • Audiology testing [ Time Frame: 3 years ]
  • Cognitive function [ Time Frame: 3 years ]
  • Tanner stage [ Time Frame: 3 years ]
  • Proteinuria [ Time Frame: 3 years ]
  • Serum creatinine [ Time Frame: 3 years ]
  • Thyroid function [ Time Frame: 3 years ]
  • Cortisol [ Time Frame: 3 years ]
  • Adrenocorticotropin hormone (ACTH) [ Time Frame: 3 years ]
  • Renin [ Time Frame: 3 years ]
  • Testosterone [ Time Frame: 3 years ]
  • Estradiol [ Time Frame: 3 years ]
  • Anti-mullerian hormone (AMH) [ Time Frame: 3 years ]
  • Inhibin B [ Time Frame: 3 years ]
  • Follicle stimulating hormone (FSH) [ Time Frame: 3 years ]
  • Luteinizing hormone (LH) [ Time Frame: 3 years ]
  • Insulin-like growth factor 1 (IGF-1) [ Time Frame: 3 years ]
  • Blood glucose [ Time Frame: 3 years ]
  • Serum sodium [ Time Frame: 3 years ]
  • Serum potassium [ Time Frame: 3 years ]
  • Serum chloride [ Time Frame: 3 years ]
  • Serum carbon dioxide (CO2) [ Time Frame: 3 years ]
  • Complete blood count [ Time Frame: 3 years ]
  • Serum immunoglobulins [ Time Frame: 3 years ]
  • Antibodies to vaccine [ Time Frame: At baseline ]
  • Blood urea nitrogen (BUN) [ Time Frame: 3 years ]
  • Patient journey questionnaire [ Time Frame: At baseline ]
  • Pediatric Quality of Life (PedsQL) Questionnaires [ Time Frame: At baseline ]
  • Cholesterol panel [ Time Frame: 3 years ]
  • Pre- and Post-Kidney Transplant Questionnaire [ Time Frame: 3 years ]
  • Echocardiography [ Time Frame: 3 years ]
  • Edema-Related Quality of Life [ Time Frame: 3 years ]
  • Patient-Reported Outcomes Measurement Information System (PROMIS) [ Time Frame: 3 years ]
  • Cystatin C [ Time Frame: 3 years ]
  • Urine specific gravity [ Time Frame: 3 years ]
  • Skin Barrier Function uingTewameter, Sebumeter, and Corneometer [ Time Frame: 3 years ]

Central Contacts and Locations

Central contacts

Julie D Saba, MD, PhD

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

Locations

University of California San Francisco

Recruiting

San Francisco, California, United States, 94143

Contacts

Julie D Saba, MD, PhD

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

Principal Investigator:

Julie D Saba, MD, PhD

More Information

Sponsor

University of California, San Francisco

Last update posted

Aug 4, 2026

Last verified

Jul, 2026

Keywords

  • sphingosine phosphate lyase
  • SGPL1
  • sphingolipidosis
  • steroid-resistant nephrotic syndrome
  • neurological defect
  • sphingolipid
  • nephrotic syndrome
  • primary adrenal insufficiency
  • primary immunodeficiency
  • Charcot-Marie-Tooth Disease
  • hypothyroidism
  • ichthyosis
  • sphingosine phosphate lyase insufficiency syndrome
  • RENI syndrome
  • NPHS14

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of California, San Francisco on 2026-08-04.