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

Study Overview
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Brief Summary
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This protocol aims to characterize the natural history of 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
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This protocol aims to characterize the natural history and create a patient registry of 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.

Official Title
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Sphingosine Phosphate Lyase Insufficiency Syndrome - Observational Study and Patient Registry (International)

Conditions
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Sphingolipidoses, Enzyme Deficiency

Intervention / Treatment
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* Other: no intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals of all ages diagnosed with SPLIS based on bi-allelic pathogenic variants of SGPL1, including children and neonates, as well as family members or caregivers, healthy volunteers and individuals with other sphingolipidoses. Exclusion Criteria: the investigators will not include: prisoners pregnant women healthy volunteers with: diabetes, infection, fever, known HIV/AIDS, cardiac disease or anemia.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Individuals with SPLIS<br>Individuals diagnosed with SPLIS based on genetic testing that confirms bi-allelic pathogenic variants in SGPL1 | Other: no intervention<br>* No interventions are involved in this observational study.<br>|
| Parents of individuals with SPLIS<br>Parents of individuals diagnosed with SPLIS based on genetic testing that confirms bi-allelic pathogenic variants in SGPL1 | Other: no intervention<br>* No interventions are involved in this observational study.<br>|
| age and gender-matched controls<br>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<br>* No interventions are involved in this observational study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | The primary outcome of this study is survival (age at death). | 0-99 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Onset of nephrotic syndrome | Age at onset of proteinuria greater than 3.5 grams per 24h | 0-99 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SGPL1, SPLIS, sphingosine phosphate lyase, sphingolipidosis, steroid-resistant nephrotic syndrome, primary adrenal insufficiency, neurological defect