講演情報
[PE4-7]Genetic heterogeneity in hyperlipidemia
○Hsu Rai-Hseng1,2, Yang Feng-Jung3,4, Chien Yin-Hsiu1,2, Lee Ni-Chung1,2, Hwu Wuh-Liang1,2 (1.Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan, 2.Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, 3.Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan, 4.School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan)
Background
Hyperlipidemia is a group of heterogenous conditions with abnormally elevated levels of lipids. The etiologies include familial hypercholesterolemia, siterolemia, lipoprotein lipase deficiency, and other rare causes like lipodystrophy. Because of the complexity of the diseases, whole exome sequencing (WES) is a powerful tool to solve the diagnosis, and to facilitate specific management.
Methods
Patients diagnosed with hyperlipidemia at National Taiwan University Hospital in recent 5 years (2017-2022) were reviewed. A total of 12 patients (7 males and 5 females) were enrolled, with a median age of 4.7 years (range, 13 days-62.7 years) at the time of molecular diagnosis. Six patients presented with hypercholesterolemia and 3 of them had xanthoma. Another 5 patients with hypertriglyceridemia had no xanthoma. One patient presented with xanthoma and borderline levels of total cholesterol and triglyceride.
Results
Four of the 6 patients with hypercholesterolemia were found with familial hypercholesterolemia (3 with LDLR mutations) and siterolemia (1 with ABCG5 mutations). Only 1 in 5 with hypertriglyceridemia had LPL mutations. However, autoantibodies were detected in 2 out of the 3 patients without a genetic finding, and hydroxychloroquine effectively decreased triglyceride levels. They were classified as autoimmune hypertriglyceridemia. The fifth patient was found with generalized lipodystrophy (BSCL2 mutation). The one with isolated xanthoma had negative genetic result. An overall diagnostic yield for hyperlipidemia was 66.7%.
Conclusion
WES is a useful tool in definitive diagnosis of hyperlipidemia. A negative finding in WES would, in the other way, suggest non-genetic etiologies, like the autoimmune hypertriglyceridemia diagnosed in this report. A precise diagnosis is critical to improve the outcome of hyperlipidemia.
Hyperlipidemia is a group of heterogenous conditions with abnormally elevated levels of lipids. The etiologies include familial hypercholesterolemia, siterolemia, lipoprotein lipase deficiency, and other rare causes like lipodystrophy. Because of the complexity of the diseases, whole exome sequencing (WES) is a powerful tool to solve the diagnosis, and to facilitate specific management.
Methods
Patients diagnosed with hyperlipidemia at National Taiwan University Hospital in recent 5 years (2017-2022) were reviewed. A total of 12 patients (7 males and 5 females) were enrolled, with a median age of 4.7 years (range, 13 days-62.7 years) at the time of molecular diagnosis. Six patients presented with hypercholesterolemia and 3 of them had xanthoma. Another 5 patients with hypertriglyceridemia had no xanthoma. One patient presented with xanthoma and borderline levels of total cholesterol and triglyceride.
Results
Four of the 6 patients with hypercholesterolemia were found with familial hypercholesterolemia (3 with LDLR mutations) and siterolemia (1 with ABCG5 mutations). Only 1 in 5 with hypertriglyceridemia had LPL mutations. However, autoantibodies were detected in 2 out of the 3 patients without a genetic finding, and hydroxychloroquine effectively decreased triglyceride levels. They were classified as autoimmune hypertriglyceridemia. The fifth patient was found with generalized lipodystrophy (BSCL2 mutation). The one with isolated xanthoma had negative genetic result. An overall diagnostic yield for hyperlipidemia was 66.7%.
Conclusion
WES is a useful tool in definitive diagnosis of hyperlipidemia. A negative finding in WES would, in the other way, suggest non-genetic etiologies, like the autoimmune hypertriglyceridemia diagnosed in this report. A precise diagnosis is critical to improve the outcome of hyperlipidemia.