Natural History of Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS)

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

28 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-04-22

Study Completion Date

2030-12-31

Brief Summary

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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.

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Detailed Description

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The main purpose of the study is to characterize the natural history of sphingosine phosphate lyase insufficiency syndrome (SPLIS) including the full spectrum of presentations (clinical, biochemical, radiological and pathological) and their change (progression or improvement) over time by collecting and analyzing data from prospective assessments on patients with SPLIS over a three-year time period and retrospective chart review of treatment history. By necessity, the investigators will also endeavor to explore the range of medical treatments and interventions currently being used in the care of SPLIS patients and their impact on the natural history of SPLIS. A retrospective arm will collect data on patients who are deceased and/or who are willing to share medical data but unwilling to participate in the prospective arm of the study.

The secondary objective of the study is to establish a set of biomarkers including plasma sphingosine-1-phosphate (S1P) and absolute lymphocyte count (ALC) that may aid in:

* Characterizing distinct phenotypic subgroups of SPLIS patients within the larger SPLIS population
* Predicting the change (progression or improvement) in symptoms of SPLIS patients over time

The exploratory objectives of the study are to explore the potential of plasma sphingolipids other than S1P, urinary sphingolipids including S1P, and immunological markers including cytokines and T cell subsets to serve as disease biomarkers. A SPLIS multi-domain responder index (MDRI) will be developed. Induced pluripotent stem cells derived from peripheral blood mononuclear cells and/or skin fibroblasts will be generated as a research tool.

Conditions

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Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS)

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

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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

no intervention

Intervention Type OTHER

No interventions are involved in this observational study.

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

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

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no intervention

No interventions are involved in this observational study.

Intervention Type OTHER

Eligibility Criteria

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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

Eligible Sex

ALL

Accepts Healthy Volunteers

No