Department of Pediatric Nephrology, Faculty of Medicine, Hacettepe University, Sihhiye, 06100, Ankara, Turkey.
Department of Pediatric Nephrology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.
Pediatr Nephrol. 2023 Mar;38(3):711-719. doi: 10.1007/s00467-022-05656-5. Epub 2022 Jun 24.
Recently, 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.
最近，编码鞘脂代谢最后一个酶的 SGPL1（鞘氨醇-1-磷酸裂解酶）的隐性突变已被报道可导致类固醇抵抗型肾病综合征、肾上腺功能不全和许多其他器官/系统受累。我们旨在确定 SGPL1 突变患者的临床和遗传特征及结局。
本研究纳入了 6 名具有双等位基因 SGPL1 突变的患者。回顾性评估了患者的临床、遗传和实验室特征及结局。我们还回顾了先前报道的具有 SGPL1 突变的患者，并与本研究中的患者进行了比较。
肾脏表现的中位年龄为 5 个月。4 名患者（67%）在 1 岁前被诊断。2 名患者的肾活检显示局灶节段性肾小球硬化，1 名患者显示弥漫性系膜硬化。3 名患者接受了类固醇治疗，但均无反应。6 名患者均进展为慢性肾脏病；5 名患者在中位年龄 6 个月时需要肾脏替代治疗。1 名患者进行了肾移植。6 名患者均存在肾上腺功能不全，其中 5 名在年龄 < 6 个月时被诊断。3 名患者存在甲状腺功能减退症，2 名患者存在鱼鳞病，4 名患者存在免疫缺陷，5 名患者存在神经学表现，2 名患者存在泌尿生殖系统异常。4 名患者在中位年龄 30.5 个月时死亡。2 名患者正在接受肾脏替代治疗。1 名患者存在新的突变。
SGPL1 突变患者的预后较差，除肾上腺功能不全外，还可出现多种类型的肾脏以外的器官/系统受累。对这类患者进行基因诊断对治疗、遗传咨询和合并症筛查非常重要。更清晰的图表摘要可在补充信息中查看。
