Clinical trial NCT04885179: SPL Insufficiency Syndrome (SPLIS)/NPHS14: a SPLIS Observational Study and Patient Registry (International)
Official title: Sphingosine Phosphate Lyase Insufficiency Syndrome - Observational Study and Patient Registry (International)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Sphingolipidoses
Enzyme Deficiency
Keywords: SPLIS
sphingosine phosphate lyase
SGPL1
sphingolipidosis
steroid-resistant nephrotic syndrome
primary adrenal insufficiency
neurological defect
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2021-05-13
Enrollment: 120
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: SPLIS is a genetic disorder caused by recessive mutations in SGPL1. The study population includes individuals with confirmed bi-allelic mutations in SGPL1, regardless of age, gender, disease manifestations, or treatments received. Some patients with SPLIS will have kidney failure, adrenal insufficiency and/or neurological problems. Parents, family members and unrelated healthy individuals enrolled during routine health appointments, elective surgical procedures and other medical interactions will be included as healthy controls.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Survival
timeFrame: 0-99 years
Secondary outcomes:
measure: Onset of nephrotic syndrome
timeFrame: 0-99 years
Other outcomes:
measure: Onset of primary adrenal insufficiency
timeFrame: 0-99 years
measure: Responsiveness of blood sphingolipid levels to vitamin B6 supplementation
timeFrame: 0-99 years
measure: Skin fibroblast sphingolipid levels in response to vitamin B6
timeFrame: 1-6 weeks
measure: Responsiveness of absolute lymphocyte count to vitamin B6 supplementation
timeFrame: 0-99 years
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Julie D Saba, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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/
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