SGPL1 Deficiency: A Rare Cause of Primary Adrenal Insufficiency
SGPL1 Deficiency: A Rare Cause of Primary Adrenal Insufficiency
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DOI：
10.1210/jc.2018-02238
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发表时间：
2019-05-01
影响因子：
5.8
通讯作者：
Stratakis, Constantine A.
中科院分区：
文献类型：
--
作者：
Settas, Nikolaos;Persky, Rebecca;Stratakis, Constantine A.
背景：多个常染色体隐性基因与原发性肾上腺皮质功能不全(PAI)的病因有关。最近，鞘氨醇-1-磷酸裂解酶1(SGPL1)基因突变被认为是导致激素抵抗型肾病综合征14型(NPHS14)的原因，NPHS14是一种具有包括PAI在内的多系统表现的鞘氨醇脂肪病。目的：探讨SGPL1基因突变是否与无肾病综合征的PAI的发病有关。方法：对21例家族性糖皮质激素病或AAA综合征患者的SGPL1基因进行测序。我们详细描述了先证者，一个沙特阿拉伯血亲父母所生的男孩，具有纯合子c.665G>；A，p.R222Q SGPL1变体。患者在2岁时出现低血糖和癫痫发作，最终被诊断为PAI(孤立性糖皮质激素缺乏)。尽管患者没有神经系统症状，但脑MRI显示基底节异常，符合退行性改变的过程。结论：PAI的新的遗传原因仍在继续被发现。我们建议，SGPL1突变的筛查不应仅限于肾病综合征患者，也可能包括缺乏NPHS14其他临床表现的PAI患者，因为在某些情况下，可能会发生肾脏疾病及其伴随特征。在肾脏功能正常的情况下，及时诊断这种特殊的鞘脂沉积症，可以迅速开始治疗，改善预后。
Context: Multiple autosomal recessive genes have been etiologically linked to primary adrenal insufficiency (PAI). Recently, sphingosine-1-phosphate lyase 1 (SGPL1) gene mutations were recognized as a cause of steroid-resistant nephrotic syndrome type 14 (NPHS14), a sphingolipidosis with multisystemic manifestations, including PAI.Objective: To check if SGPL1 mutations are involved in the pathogenesis of PAI in patients who do not exhibit nephrotic syndrome.Methods: Sequencing of the SGPL1 gene in 21 patients with familial glucocorticoid disease or triple A syndrome.Results: We identified two missense SGPL1 variants in four patients, two of whom were first cousins. We describe in detail the proband, a boy born to Saudi Arabian consanguineous parents with a homozygous c.665G>A, p.R222Q SGPL1 variant. The patient presented with hypoglycemia and seizures at age 2 years and was ultimately diagnosed with PAI (isolated glucocorticoid deficiency). Brain MRI showed abnormalities in the basal ganglia consistent with a degenerative process albeit the patient had no neurologic symptoms.Conclusions: New genetic causes of PAI continue to be identified. We suggest that screening for SGPL1 mutations should not be reserved only for patients with nephrotic syndrome but may also include patients with PAI who lack other clinical manifestations of NPHS14 because, in certain cases, kidney disease and accompanying features might develop. Timely diagnosis of this specific sphingolipidosis while the kidneys still function normally can lead to prompt initiation of therapy and improve outcome.