Unit of Endocrinology, Bambino Gesù Children's Hospital, Rome, Italy.
Rare and Complex Epilepsy, Department of Neuroscience, Bambino Gesù Children Hospital, Rome, Italy.
Ital J Pediatr. 2020 Oct 24;46(1):158. doi: 10.1186/s13052-020-00916-2.
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.
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.
Metreleptin may be used to control metabolic disturbances and may lead to better seizure control in children with PELD.
已经发现了许多与 BSCL2/seipin 基因变异相关的遗传综合征。导致外显子 7 跳跃的变异与进行性肌阵挛性癫痫伴/不伴脂肪营养不良（PELD）有关，其特征是在幼年时出现进行性肌阵挛性癫痫、严重进行性神经功能障碍和早逝，通常在儿童时期。由于 PELD 的遗传基础与 2 型先天性脂肪营养不良相似，我们假设 PELD 患者可能对其他先天性脂肪营养不良综合征批准的治疗有反应。
我们描述了一名 5 岁男孩，他患有一种极其罕见的表型，涉及严重进行性肌阵挛性癫痫，他接受 metreleptin（瘦素的重组类似物）治疗以控制代谢异常。他在两岁时没有皮下脂肪组织，伴有高甘油三酯血症、高转氨酶血症和肝脂肪变性。他还有中度精神运动发育迟缓及全身性强直阵挛性癫痫发作。在 4 岁时，他出现胰岛素抵抗、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；他开始接受降脂饮食。明显存在严重的精神运动发育迟缓、肌阵挛/肌阵挛性失神发作。在 5 岁时，开始给予 metreleptin 0.06mg/kg/天；2 个月后，患者的血脂谱改善，胰岛素抵抗得到解决。治疗 1 年后，肝脂肪变性改善，腹部超声仅显示轻度肝肿大。癫痫发作频率减少，但在 metreleptin 治疗期间并未消除。
metreleptin 可用于控制代谢紊乱，并可能导致 PELD 儿童更好地控制癫痫发作。
