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

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.

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.