PDF(Pubmed)
Abstract：
Systemic autoinflammatory diseases (SAIDs) are a group of disorders that constitute a rare cause of recurrent fevers. Recurrent fevers are defined as periodic febrile episodes lasting from days to weeks, separated by symptom-free intervals of variable duration. They present multiple etiologies, representing a diagnostic challenge. Mevalonate kinase deficiency (MKD) is a genetic SAID, a rare hereditary recurrent fever syndrome (HRF) caused by pathogenic variants in the mevalonate kinase (MVK) gene. It is characterized by the early onset of periodic fever flares, frequently associated with joint, gastrointestinal, skin, and lymph node involvement. Although elevated serum immunoglobulin D (IgD) levels were previously considered an MKD\'s hallmark, normal values do not exclude it. High serum immunoglobulin A (IgA) is frequent. An acute-phase response and elevated urinary mevalonic acid (UAV) excretion during flares may aid in the diagnosis. Genetic testing is an essential tool to confirm the diagnosis. The authors report two siblings presenting with early infancy onset of recurrent febrile illness and characteristic associated symptoms, one of which was initially misdiagnosed with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. MKD diagnoses were only established at 12 and nine years old, respectively, after the identification of the same two MVKgene variants. The diagnosis in the eldest favored the earlier recognition of MKD in the youngest. Owing to its wide spectrum of manifestations, with many being nonspecific and/or shared with other more frequent entities, a significant proportion of MKD patients present a long delay until its final establishment. These cases illustrate the MKD diagnosis and management\'s difficulties, reinforcing the importance of a careful clinical history and HRF awareness for its prompt diagnosis and appropriate precocious referral.
摘要：
全身性自身炎性疾病(SAID)是一组构成复发性发热的罕见原因的疾病。反复发热被定义为持续数天至数周的周期性发热发作，由可变持续时间的无症状间隔分开。他们提出了多种病因，代表诊断挑战。甲羟戊酸激酶缺乏症（MKD）是一种遗传性SAID，一种由甲羟戊酸激酶（MVK）基因致病变异引起的罕见遗传性复发性发热综合征（HRF）。它的特点是早期发作的周期性发热耀斑，经常与关节相关，胃肠,皮肤,淋巴结受累.尽管血清免疫球蛋白D（IgD）水平升高以前被认为是MKD的标志，正常值不排除它。高血清免疫球蛋白A（IgA）是常见的。耀斑期间的急性期反应和尿甲羟戊酸（UAV）排泄升高可能有助于诊断。基因检测是确认诊断的重要工具。作者报告了两个兄弟姐妹，他们在婴儿期早期出现复发性发热疾病和特征性相关症状，其中一个最初被误诊为周期性发烧，口疮性口炎，咽炎,和甲状腺炎（PFAPA）综合征。MKD诊断仅在12岁和9岁时确定，分别,在鉴定相同的两个MVK基因变体之后。年龄最大的诊断有利于较早地认识到年龄最小的MKD。由于其广泛的表现形式，其中许多是非特定的和/或与其他更频繁的实体共享的，相当比例的MKD患者出现了很长时间的延迟,直到其最终建立.这些病例说明了MKD诊断和管理的困难，加强仔细的临床病史和HRF意识对于其及时诊断和适当的早熟转诊的重要性。
