Thyroid and Metabolic Diseases Unit, Biomedical Research Institute (CIMUS)-IDIS, School of Medicine, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
Division of Endocrinology and Nutrition, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
Eur J Hum Genet. 2018 Mar;26(3):396-406. doi: 10.1038/s41431-017-0052-8. Epub 2018 Jan 24.
Celia's encephalopathy (progressive encephalopathy with/without lipodystrophy, PELD) is a recessive neurodegenerative disease that is fatal in childhood. It is caused by a c.985C>T variant in the BSCL2/seipin gene that results in an aberrant seipin protein. We evaluated neurological development before and during treatment with human recombinant leptin (metreleptin) plus a dietary intervention rich in polyunsaturated fatty acids (PUFA) in the only living patient. A 7 years and 10 months old girl affected by PELD was treated at age 3 years with metreleptin, adding at age 6 omega-3 fatty acid supplementation. Her mental age was evaluated using the Battelle Developmental Inventory Screening Test (BDI), and brain PET/MRI was performed before treatment and at age 5, 6.5, and 7.5 years. At age 7.5 years, the girl remains alive and leads a normal life for her mental age of 30 months, which increased by 4 months over the last 18 months according to BDI. PET images showed improved glucose uptake in the thalami, cerebellum, and brainstem. This patient showed a clear slowdown in neurological regression during leptin replacement plus a high PUFA diet. The aberrant BSCL2 transcript was overexpressed in SH-SY5Y cells and was treated with docosahexaenoic acid (200 µM) plus leptin (0.001 mg/ml) for 24 h. The relative expression of aberrant BSCL2 transcript was measured by qPCR. In vitro studies showed significant reduction (32%) in aberrant transcript expression. This therapeutic approach should be further studied in this devastating disease.
赛莉娅脑病（伴或不伴脂肪营养不良的进行性脑病，PELD）是一种隐性神经退行性疾病，在儿童期致命。它是由 BSCL2/ seipin 基因中的 c.985C>T 变体引起的，导致异常的 seipin 蛋白。我们评估了唯一存活患者在接受人重组瘦素（metreleptin）联合富含多不饱和脂肪酸（PUFA）饮食干预治疗前后的神经发育情况。一名 7 岁 10 个月大的女孩患有 PELD，在 3 岁时接受 metreleptin 治疗，在 6 岁时添加 omega-3 脂肪酸补充剂。她的智力年龄使用 Battelle 发育库存筛查测试（BDI）进行评估，并在治疗前和 5 岁、6.5 岁和 7.5 岁时进行大脑 PET/MRI。在 7.5 岁时，女孩仍然活着，过着正常的生活，其智力年龄为 30 个月，根据 BDI，过去 18 个月增加了 4 个月。PET 图像显示丘脑、小脑和脑干的葡萄糖摄取增加。在瘦素替代加高 PUFA 饮食治疗后，该患者的神经退行性病变明显减缓。异常的 BSCL2 转录本在 SH-SY5Y 细胞中过度表达，并在 docosahexaenoic acid（200µM）和瘦素（0.001mg/ml）处理 24 小时后进行治疗。通过 qPCR 测量异常 BSCL2 转录本的相对表达。体外研究表明异常转录本表达显著减少（32%）。这种治疗方法应在这种毁灭性疾病中进一步研究。
