Theodoropoulos Panagiotis, Fanaropoulou Nina Maria, Manessis Anastasios
Department of Endocrinology, Endocrine Associates of West Village, New York City, New York.
Department of Medicine, NYU Grossman School of Medicine, New York City, New York.
AACE Clin Case Rep. 2024 Aug 22;10(6):240-243. doi: 10.1016/j.aace.2024.08.006. eCollection 2024 Nov-Dec.
BACKGROUND/OBJECTIVE: Genetic causes of hypertriglyceridemia like familial chylomicronemia syndrome can be overlooked in everyday practice. We report a patient with a rare genetic mutation, highlighting the importance of genetic testing for timely diagnosis and prevention of complications.
A 45-year-old Hispanic female presented with serum triglyceride levels of 749 mg/dL, refractory to rosuvastatin 10 mg daily and omega-3 ethyl esters 2 g daily. Initial studies showed total cholesterol of 278 mg/dL and high-density lipoprotein of 38 mg/dL. Physical examination was negative for hepatosplenomegaly and xanthoma, with no reported history of acute pancreatitis. Despite treatment escalation with gemfibrozil, fenofibrate, and icosapent ethyl, her triglyceride levels remained elevated, peaking at 4300 mg/dL. Seven years after presentation, genetic testing revealed homozygosity for c.11delC of the apolipoprotein A5 gene, confirming the diagnosis of familial chylomicronemia syndrome. Postdiagnosis, the patient adhered to a strict low-fat diet with daily fat intake of less than 15-20 g, limited simple sugars, refined carbohydrates, and alcohol, leading to a nadir of serum triglycerides of 197 mg/dL.
The identified mutation is exceedingly rare (<0.01%), as most associated mutations involve the lipoprotein lipase gene. There are no approved therapies for genetic hypertriglyceridemia. The mainstay of treatment is a very low-fat diet to prevent complications.
We underscore the importance of genetic testing in refractory hypertriglyceridemia despite a lack of clinical signs. A definitive diagnosis can alleviate patient burden, improve therapeutic adherence, and enhance the patient-physician relationship.
背景/目的：在日常临床实践中，像家族性乳糜微粒血症综合征这样的高甘油三酯血症的遗传病因可能会被忽视。我们报告了一名患有罕见基因突变的患者，强调了基因检测对于及时诊断和预防并发症的重要性。
一名45岁的西班牙裔女性，血清甘油三酯水平为749mg/dL，对每日10mg瑞舒伐他汀和每日2gω-3乙酯治疗无效。初始检查显示总胆固醇为278mg/dL，高密度脂蛋白为38mg/dL。体格检查未发现肝脾肿大和黄瘤，也没有急性胰腺炎病史。尽管使用吉非贝齐、非诺贝特和二十碳五烯酸乙酯加强治疗，她的甘油三酯水平仍居高不下，最高达到4300mg/dL。就诊7年后，基因检测显示载脂蛋白A5基因c.11delC纯合突变，确诊为家族性乳糜微粒血症综合征。确诊后，患者坚持严格的低脂饮食，每日脂肪摄入量少于15 - 20g，限制单糖、精制碳水化合物和酒精摄入，血清甘油三酯最低降至197mg/dL。
所发现的突变极为罕见（<0·01%），因为大多数相关突变涉及脂蛋白脂肪酶基因。目前尚无获批用于治疗遗传性高甘油三酯血症的疗法。治疗的主要方法是极低脂饮食以预防并发症。
我们强调，尽管缺乏临床症状，但基因检测在难治性高甘油三酯血症中具有重要意义。明确的诊断可以减轻患者负担，提高治疗依从性，并增进医患关系。
