Enzyme Deficiency, Sphingolipidoses
Conditions
Keywords
SPLIS, sphingosine phosphate lyase, SGPL1, sphingolipidosis, steroid-resistant nephrotic syndrome, primary adrenal insufficiency, neurological defect
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.
Interventions
OTHERno intervention
No interventions are involved in this observational study.
Sponsors
University of California, San Francisco
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival | 0-99 years | The primary outcome of this study is survival (age at death). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Onset of nephrotic syndrome | 0-99 years | Age at onset of proteinuria greater than 3.5 grams per 24h |
Other
| Measure | Time frame | Description |
|---|---|---|
| Onset of primary adrenal insufficiency | 0-99 years | Age at onset of glucocorticoid insufficiency with or without other endocrine defects |
| Responsiveness of blood sphingolipid levels to vitamin B6 supplementation | 0-99 years | Changes in blood sphingolipid levels before and after caring physician-initiated vitamin B6 supplementation |
| Skin fibroblast sphingolipid levels in response to vitamin B6 | 1-6 weeks | Skin fibroblast sphingolipid levels compared by liquid chromatography/mass spectrometry in medium containing various forms of vitamin B6 or lacking vitamin B6. |
| Responsiveness of absolute lymphocyte count to vitamin B6 supplementation | 0-99 years | Changes in blood absolute lymphocyte count before and after caring physician-initiated vitamin B6 |
Countries
United States
Contacts
Primary ContactJulie D Saba, MD, PhD
Backup ContactJoanna Y Lee, PhD
Outcome results
None listed