Tanaka Takayuki, Yoshioka Kohei, Nishikomori Ryuta, Sakai Hidemasa, Abe Junya, Yamashita Yuriko, Hiramoto Ryugo, Morimoto Akira, Ishii Eiichi, Arakawa Hirokazu, Kaneko Utako, Ohshima Yusei, Okamoto Nami, Ohara Osamu, Hata Ikue, Shigematsu Yosuke, Kawai Tomoki, Yasumi Takahiro, Heike Toshio
a Department of Pediatrics , Kyoto University Graduate School of Medicine , Kyoto , Japan.
b Department of Pediatrics , Kitano Hospital, Tazuke Kofukai Medical Research Institute , Osaka , Japan.
Mod Rheumatol. 2019 Jan;29(1):181-187. doi: 10.1080/14397595.2018.1442639. Epub 2018 Mar 2.
Mevalonate kinase deficiency (MKD), a rare autosomal recessive autoinflammatory syndrome, is caused by disease-causing variants of the mevalonate kinase (MVK) gene. A national survey was undertaken to investigate clinical and genetic features of MKD patients in Japan.
The survey identified ten patients with MKD. Clinical information and laboratory data were collected from medical records and by direct interviews with patients, their families, and their attending physicians. Genetic analysis and measurement of MVK activity and urinary excretion of mevalonic acid were performed.
None of the 10 patients harbored MVK disease-causing variants that are common in European patients. However, overall symptoms were in line with previous European reports. Continuous fever was observed in half of the patients. Elevated transaminase was observed in four of the 10 patients, two of whom fulfilled the diagnostic criteria for hemophagocytic lymphohistiocytosis. About half of the patients responded to temporary administration of glucocorticoids and NSAIDs; the others required biologics such as anti-IL-1 drugs.
This is the first national survey of MKD patients in a non-European country. Although clinical symptoms were similar to those reported in Europe, the incidence of continuous fever and elevated transaminase was higher, probably due to differences in disease-causing variants.
甲羟戊酸激酶缺乏症（MKD）是一种罕见的常染色体隐性自身炎症综合征，由甲羟戊酸激酶（MVK）基因的致病变体引起。在日本开展了一项全国性调查，以研究MKD患者的临床和遗传特征。
该调查确定了10例MKD患者。从病历以及通过直接访谈患者、其家人和主治医生收集临床信息和实验室数据。进行了基因分析、MVK活性测定以及甲羟戊酸的尿排泄量测定。
这10例患者均未携带在欧洲患者中常见的MVK致病变体。然而，总体症状与先前欧洲的报告一致。半数患者出现持续发热。10例患者中有4例转氨酶升高，其中2例符合噬血细胞性淋巴组织细胞增生症的诊断标准。约半数患者对短期使用糖皮质激素和非甾体抗炎药有反应；其他患者需要使用抗IL-1药物等生物制剂。
这是在非欧洲国家首次对MKD患者进行的全国性调查。尽管临床症状与欧洲报告的相似，但持续发热和转氨酶升高的发生率更高，可能是由于致病变体的差异所致。
