OBJECTIVE This review will summarize current knowledge on the burden of illness (BOI) in tuberous sclerosis complex (TSC), a multisystem genetic disorder manifesting with hamartomas throughout the body, including mainly the kidneys, brain, skin, eyes, heart, and lungs. METHODS We performed a systematic analysis of the available literature on BOI in TSC according to the PRISMA guidelines. All studies irrespective of participant age that reported on individual and societal measures of disease burden (e.g. health care resource use, costs, quality of life) were included. RESULTS We identified 33 studies reporting BOI in TSC patients. Most studies (21) reported health care resource use, while 14 studies reported quality of life and 10 studies mentioned costs associated with TSC. Only eight research papers reported caregiver BOI. Substantial BOI occurs from most manifestations of the disorder, particularly from pharmacoresistant epilepsy, neuropsychiatric, renal and skin manifestations. While less frequent, pulmonary complications also lead to a high individual BOI. The range for the mean annual direct costs varied widely between 424 and 98,008 International Dollar purchasing power parities (PPP-$). Brain surgery, end-stage renal disease with dialysis, and pulmonary complications all incur particularly high costs. There is a dearth of information regarding indirect costs in TSC. Mortality overall is increased compared to general population; and most TSC related deaths occur as a result of complications from seizures as well as renal complications. Long term studies report mortality between 4.8 and 8.3% for a follow-up of 8 to 17.4 years. CONCLUSIONS TSC patients and their caregivers have a high burden of illness, and TSC patients incur high costs in health care systems. At the same time, the provision of inadequate treatment that does not adhere to published guidelines is common and centralized TSC care is received by no more than half of individuals who need it, especially adults. Further studies focusing on the cost effectiveness and BOI outcomes of coordinated TSC care as well as of new treatment options such as mTOR inhibitors are necessary.

中文翻译：

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对结节性硬化症（TSC）患者疾病负担的系统评价。

目的本综述将总结目前对结节性硬化症（TSC）中疾病负担（BOI）的知识，结节性硬化症是一种多系统遗传病，表现为遍布全身的错构瘤，主要包括肾脏，大脑，皮肤，眼睛，心脏和肺部。方法我们根据PRISMA指南对TSC中BOI的可用文献进行了系统分析。不论参与者年龄如何，所有研究均报告了疾病负担的个人和社会衡量指标（例如，卫生保健资源的使用，成本，生活质量）。结果我们确定了33项报告TSC患者BOI的研究。大多数研究（21）报告了医疗资源的使用，而14个研究报告了生活质量，还有10个研究提到与TSC相关的费用。只有八篇研究报告报道了照顾者BOI。大量的BOI发生于该疾病的大多数表现，尤其是耐药性癫痫，神经精神病，肾脏和皮肤表现。肺部并发症虽然不那么频繁，但也会导致较高的个人BOI。年平均直接成本范围在424至98,008国际美元购买力平价（PPP- $）之间。脑外科手术，终末期肾脏疾病伴透析和肺部并发症均招致特别高的费用。在TSC中缺乏有关间接费用的信息。与总人口相比，总的死亡率增加了；大多数与TSC相关的死亡都是由癫痫发作引起的并发症以及肾脏并发症引起的。长期研究报告，随访8至17.4年，死亡率在4.8％至8.3％之间。结论TSC患者及其护理人员的疾病负担很高，TSC患者的医疗保健系统费用较高。同时，提供不符合已发布指南的不充分治疗是很普遍的，集中式TSC护理的接受者不超过一半，尤其是成年人。进一步研究的重点是协调TSC护理以及新的治疗选择（例如mTOR抑制剂）的成本效益和BOI结果。