Tugba Tastemel Ozturk, Nur Canpolat, Seha Saygili, Umut Selda Bayrakci, Oguz Soylemezoglu, Fatih Ozaltin, Rezan Topaloglu
Pediatric nephrology (Berlin, Germany) 2023 MarRecently, recessive mutations in SGPL1 (sphingosine-1-phosphate lyase), which encodes the final enzyme of sphingolipid metabolism, have been reported to cause steroid-resistant nephrotic syndrome, adrenal insufficiency, and many other organ/system involvements. We aimed to determine the clinical and genetic characteristics, and outcomes in patients with SGPL1 mutations. The study included 6 patients with bi-allelic SGPL1 mutation. Clinical, genetic, and laboratory characteristics, and outcomes of the patients were evaluated retrospectively. We also reviewed previously reported patients with SGPL1 mutations and compared them to the presented patients. The median age at kidney presentation was 5 months. Four patients (67%) were diagnosed before age 1 year. Kidney biopsy showed focal segmental glomerulosclerosis in 2 patients and diffuse mesangial sclerosis in one patient. Steroids were given to 3 patients, but they did not respond. All 6 patients progressed to chronic kidney disease; 5 required kidney replacement therapy (KRT) at a median age of 6 months. Deceased kidney transplantation was performed in one patient. All 6 patients had adrenal insufficiency, of which 5 were diagnosed at age < 6 months. Three patients had hypothyroidism, 2 had ichthyosis, 4 had immunodeficiency, 5 had neurological findings, and 2 had genitourinary system anomalies. Four patients died at a median age of 30.5 months. Two patients are being followed up with KRT. One patient had a novel mutation. Patients with SGPL1 mutations have a poor prognosis, and many types of extrarenal organ/system involvement beyond adrenal insufficiency can be seen. Genetic diagnosis of such patients is important for treatment, genetic counseling, and screening for comorbid conditions. A higher resolution version of the Graphical abstract is available as Supplementary information. © 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.
Tugba Tastemel Ozturk, Nur Canpolat, Seha Saygili, Umut Selda Bayrakci, Oguz Soylemezoglu, Fatih Ozaltin, Rezan Topaloglu. A rare cause of nephrotic syndrome-sphingosine-1-phosphate lyase (SGPL1) deficiency: 6 cases and a review of the literature. Pediatric nephrology (Berlin, Germany). 2023 Mar;38(3):711-719
PMID: 35748945
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