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Abstract：
BACKGROUND: A number of genetic syndromes associated with variants in the BSCL2/seipin gene have been identified. Variants that cause skipping of exon 7 are associated with progressive encephalopathy with/without lipodystrophy (PELD), which is characterized by the development of progressive myoclonic epilepsy at a young age, severe progressive neurological impairment, and early death, often in childhood. Because the genetic basis of PELD is similar to that of congenital lipodystrophy type 2, we hypothesized that a patient with PELD may respond to treatments approved for other congenital lipodystrophic syndromes.
METHODS: We describe a 5-year-old boy with an extremely rare phenotype involving severe progressive myoclonic epilepsy who received metreleptin (a recombinant analogue of leptin) to control metabolic abnormalities. At the age of two, he had no subcutaneous adipose tissue, with hypertriglyceridemia, hypertransaminasemia and hepatic steatosis. He also had a moderate psychomotor delay and generalized tonic seizures. At 4 years, he had insulin resistance, hypercholesterolemia, hypertriglyceridemia, mild hepatosplenomegaly and mild hepatic steatosis; he began a hypolipidemic diet. Severe psychomotor delay and myoclonic/myoclonic atonic seizures with absences was evident. At 5 years of age, metreleptin 0.06 mg/kg/day was initiated; after 2 months, the patient\'s lipid profile improved and insulin resistance resolved. After 1 year of treatment, hepatic steatosis improved and abdominal ultrasound showed only mild hepatomegaly. Seizure frequency decreased but was not eliminated during metreleptin therapy.
CONCLUSIONS: Metreleptin may be used to control metabolic disturbances and may lead to better seizure control in children with PELD.
METHODS: We describe a 5-year-old boy with an extremely rare phenotype involving severe progressive myoclonic epilepsy who received metreleptin (a recombinant analogue of leptin) to control metabolic abnormalities. At the age of two, he had no subcutaneous adipose tissue, with hypertriglyceridemia, hypertransaminasemia and hepatic steatosis. He also had a moderate psychomotor delay and generalized tonic seizures. At 4 years, he had insulin resistance, hypercholesterolemia, hypertriglyceridemia, mild hepatosplenomegaly and mild hepatic steatosis; he began a hypolipidemic diet. Severe psychomotor delay and myoclonic/myoclonic atonic seizures with absences was evident. At 5 years of age, metreleptin 0.06 mg/kg/day was initiated; after 2 months, the patient\'s lipid profile improved and insulin resistance resolved. After 1 year of treatment, hepatic steatosis improved and abdominal ultrasound showed only mild hepatomegaly. Seizure frequency decreased but was not eliminated during metreleptin therapy.
CONCLUSIONS: Metreleptin may be used to control metabolic disturbances and may lead to better seizure control in children with PELD.
摘要：
背景：已经鉴定了许多与BSCL2/seipin基因变异相关的遗传综合征。导致外显子7跳过的变异与有/没有脂肪营养不良（PELD）的进行性脑病有关，其特征是在年轻时发展为进行性肌阵挛性癫痫，严重的进行性神经功能缺损，早逝,往往在童年。由于PELD的遗传基础与2型先天性脂肪营养不良相似，因此我们假设PELD患者可能对批准用于其他先天性脂肪营养不良综合征的治疗有反应。
方法：我们描述了一个5岁男孩，他的表型极为罕见，涉及严重的进行性肌阵挛性癫痫，他接受了metreleptin（一种瘦素的重组类似物）来控制代谢异常。两岁时，他没有皮下脂肪组织,高甘油三酯血症，高转氨酶血症和肝性脂肪变性。他还患有中度精神运动延迟和全身性强直性癫痫发作。四年后，他有胰岛素抵抗，高胆固醇血症,高甘油三酯血症,轻度肝脾肿大和轻度肝脂肪变性；他开始降血脂饮食。严重的精神运动延迟和肌阵挛性/肌阵挛性失速癫痫发作伴缺勤是明显的。在5岁的时候，开始使用metreleptin0.06mg/kg/天；2个月后，患者的血脂状况得到改善，胰岛素抵抗得到缓解。治疗1年后,肝脂肪变性改善，腹部超声仅显示轻度肝肿大。在metreleptin治疗期间，癫痫发作频率降低，但未消除。
结论：Metreleptin可用于控制代谢紊乱，并可能导致PELD患儿更好地控制癫痫发作。
方法：我们描述了一个5岁男孩，他的表型极为罕见，涉及严重的进行性肌阵挛性癫痫，他接受了metreleptin（一种瘦素的重组类似物）来控制代谢异常。两岁时，他没有皮下脂肪组织,高甘油三酯血症，高转氨酶血症和肝性脂肪变性。他还患有中度精神运动延迟和全身性强直性癫痫发作。四年后，他有胰岛素抵抗，高胆固醇血症,高甘油三酯血症,轻度肝脾肿大和轻度肝脂肪变性；他开始降血脂饮食。严重的精神运动延迟和肌阵挛性/肌阵挛性失速癫痫发作伴缺勤是明显的。在5岁的时候，开始使用metreleptin0.06mg/kg/天；2个月后，患者的血脂状况得到改善，胰岛素抵抗得到缓解。治疗1年后,肝脂肪变性改善，腹部超声仅显示轻度肝肿大。在metreleptin治疗期间，癫痫发作频率降低，但未消除。
结论：Metreleptin可用于控制代谢紊乱，并可能导致PELD患儿更好地控制癫痫发作。
