Maharaj Avinaash, Güran Tülay, Buonocore Federica, Achermann John C, Metherell Louise, Prasad Rathi, Çetinkaya Semra
Centre for Endocrinology, William Harvey Research Institute, John Vane Science Centre, Queen Mary, University of London, Charterhouse Square, London, United Kingdom.
Marmara University, School of Medicine, Department of Paediatric Endocrinology and Diabetes, Istanbul, Turkey.
J Endocr Soc. 2022 Feb 11;6(5):bvac020. doi: 10.1210/jendso/bvac020. eCollection 2022 May 1.
Sphingosine-1-phosphate lyase (SGPL1) insufficiency syndrome (SPLIS) is a multisystemic disorder which, in the main, incorporates steroid-resistant nephrotic syndrome and primary adrenal insufficiency (PAI).
We present a young girl with a novel homozygous variant in , p.D350G, with PAI in the absence of nephrotic syndrome. In the course of 15 years of follow-up she has further developed primary hypothyroidism and while she has progressed through puberty appropriately, ovarian calcifications were noted on imaging. The p.D350G variant results in reduced protein expression of SGPL1. We demonstrate that CRISPR engineered knockout of in human adrenocortical (H295R) cells abrogates cortisol production. Furthermore, while wild-type SGPL1 is able to rescue cortisol production in this in vitro model of adrenal disease, this is not observed with the p.D350G mutant.
SGPL1 deficiency should be considered in the differential diagnosis of PAI with close attention paid to evolving disease on follow-up.
鞘氨醇-1-磷酸裂解酶（SGPL1）功能不全综合征（SPLIS）是一种多系统疾病，主要包括类固醇抵抗型肾病综合征和原发性肾上腺皮质功能减退症（PAI）。
我们报告一名年轻女孩，其 基因存在一种新的纯合变异，即 p.D350G，患有原发性肾上腺皮质功能减退症但无肾病综合征。在 15 年的随访过程中，她进一步发展为原发性甲状腺功能减退症，虽然她青春期发育正常，但影像学检查发现卵巢钙化。p.D350G 变异导致 SGPL1 蛋白表达降低。我们证明，在人肾上腺皮质（H295R）细胞中通过 CRISPR 技术敲除 可消除皮质醇的产生。此外，虽然野生型 SGPL1 能够在这种肾上腺疾病的体外模型中挽救皮质醇的产生，但 p.D350G 突变体却不能。
在原发性肾上腺皮质功能减退症的鉴别诊断中应考虑 SGPL1 缺乏症，并在随访中密切关注病情的进展。
