Sinnott Bridget P, Mazzone Theodore
Division of Endocrinology, University of Illinois, Chicago, Illinois 60612, USA.
Endocr Pract. 2006 Mar-Apr;12(2):183-7. doi: 10.4158/EP.12.2.183.
To describe a patient with tuberous xanthomas and high levels of cholesterol and triglycerides, who was found to have type III hyperlipoproteinemia (HLP) and a rare apolipoprotein E (apoE) mutation.
We present a case report with extensive clinical, laboratory, and genetic documentation.
A 33-year-old African American man presented for evaluation of hypertriglyceridemia. His medical history was remarkable for schizophrenia necessitating ongoing olanzapine therapy for the past 6 years. A few months after olanzapine treatment was begun, he noted the development of nontender, firm, papular skin lesions on his elbows and knees. His family history was negative for lipid disorders or premature vascular disease. Physical examination revealed the presence of prominent tuberous xanthomas on both elbows and knees. Results of a lipid panel demonstrated a total cholesterol level of 374 mg/dL (9.7 mmol/L) and triglycerides of 828 mg/dL (9.3 mmol/L). A work-up for causes of secondary hyper-triglyceridemia was negative. Results of apoE genotyping by a commercial laboratory showed the E3/E3 genotype, based on gene sequencing at codons 112 and 158. Because the skin lesions were typical for type III HLP, his entire apoE gene was sequenced. This analysis revealed an apoE2/E2 (arginine 145 to cysteine) mutation, previously reported to be a rare cause of type III HLP in 5 patients of African descent. Triglyceride-lowering therapy with gem-fibrozil was initiated, in addition to lifestyle modification. At follow-up several months later, total cholesterol was 276 mg/dL (7.14 mmol/L) and triglycerides were 479 mg/dL (5.41 mmol/L).
We speculate that olanzapine therapy, with its known metabolic side effects, exacerbated this patient's underlying lipoprotein metabolic abnormality. To our knowledge, this is the first report of an association between olanzapine therapy and tuberous xanthomas and the sixth report of this rare apoE2/E2 (arginine 145 to cysteine) mutation in the literature.
描述一名患有结节性黄瘤且胆固醇和甘油三酯水平升高的患者，该患者被发现患有III型高脂蛋白血症（HLP）及一种罕见的载脂蛋白E（apoE）突变。
我们呈现一份包含广泛临床、实验室及基因记录的病例报告。
一名33岁的非裔美国男性因高甘油三酯血症前来评估。他有精神分裂症病史，在过去6年里一直需要使用奥氮平进行治疗。奥氮平治疗开始几个月后，他注意到肘部和膝部出现了无痛、坚硬的丘疹样皮肤病变。他的家族史中无脂质紊乱或早发性血管疾病。体格检查发现双肘和双膝有明显的结节性黄瘤。血脂检查结果显示总胆固醇水平为374 mg/dL（9.7 mmol/L），甘油三酯为828 mg/dL（9.3 mmol/L）。对继发性高甘油三酯血症病因的检查结果为阴性。一家商业实验室进行的apoE基因分型结果显示，基于密码子112和158处的基因测序，其基因型为E3/E3。由于皮肤病变符合III型HLP的典型表现，因此对他的整个apoE基因进行了测序。该分析揭示了一种apoE2/E2（精氨酸145突变为半胱氨酸）突变，此前在5名非洲裔患者中曾报道这是III型HLP的一种罕见病因。除了改变生活方式外，还开始使用吉非贝齐进行降甘油三酯治疗。几个月后的随访中，总胆固醇为276 mg/dL（7.14 mmol/L），甘油三酯为479 mg/dL（5.41 mmol/L）。
我们推测，已知具有代谢副作用的奥氮平治疗加剧了该患者潜在的脂蛋白代谢异常。据我们所知，这是奥氮平治疗与结节性黄瘤之间关联的首例报告，也是文献中关于这种罕见的apoE2/E2（精氨酸145突变为半胱氨酸）突变的第六例报告。
