Takayuki Tanaka1, Kohei Yoshioka1, Ryuta Nishikomori1, Hidemasa Sakai1, Junya Abe1,2, Yuriko Yamashita3, Ryugo Hiramoto3, Akira Morimoto4, Eiichi Ishii5, Hirokazu Arakawa6, Utako Kaneko7, Yusei Ohshima8, Nami Okamoto9, Osamu Ohara10, Ikue Hata8, Yosuke Shigematsu8, Tomoki Kawai1, Takahiro Yasumi1, Toshio Heike1. 1. a Department of Pediatrics , Kyoto University Graduate School of Medicine , Kyoto , Japan. 2. b Department of Pediatrics , Kitano Hospital, Tazuke Kofukai Medical Research Institute , Osaka , Japan. 3. c Department of Pediatrics , Matsudo City General Hospital Children's Medical Centre , Matsudo , Japan. 4. d Department of Pediatrics , Jichi Medical University of School of Medicine , Shimotsuke , Japan. 5. e Department of Pediatrics , Ehime University Graduate School of Medicine , Toon , Japan. 6. f Department of Pediatrics , Gumma University Graduate School of Medicine , Maebashi , Japan. 7. g Department of Pediatrics , Niigata University Graduate School of Medical and Dental Sciences , Niigata , Japan. 8. h Department of Pediatrics, Faculty of Medical Sciences , University of Fukui , Fukui , Japan. 9. i Department of Pediatrics , Osaka Medical College , Takatsuki , Japan. 10. j Department of Technology, Kazusa DNA Research Institute , Chiba , Japan.
Abstract
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Entities:
Keywords:
Canakinumab; genotype-phenotype relationship; mevalonate kinase deficiency; national survey
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