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Early canakinumab therapy for the sensorineural deafness in a family with Muckle-Wells syndrome due to a novel mutation of NLRP3 gene

  • Yasunori Iida
  • Hiroyuki Wakiguchi
  • Fumiko Okazaki
  • Tamaki Nakamura
  • Hiroki Yasudo
  • Makoto Kubo
  • Kazuma Sugahara
  • Hiroshi Yamashita
  • Yutaka Suehiro
  • Naoko Okayama
  • Kunio Hashimoto
  • Naoki Iwamoto
  • Atsushi Kawakami
  • Yoshiharu Aoki
  • Hidetoshi Takada
  • Shouichi Ohga
  • Shunji Hasegawa
Brief Report

Abstract

Cryopyrin-associated periodic syndrome (CAPS) is one of the autoinflammatory disorders caused by mutations in NLRP3 gene. The over-production of interleukin (IL)-1β induced by NLRP3 gene mutations plays an important role in the pathophysiology of CAPS. We diagnosed 3 patients with CAPS, who were lineal family members having a novel mutation of NLRP3 gene. The objective of this report is to compare the characteristics of symptoms and differences in the therapeutic responses of them, who had the same mutation. In addition, we aimed to examine the usefulness of cytokine measurement for diagnosis or determination of treatment effect of CAPS. A 5-year-old Japanese boy (proband) came to our hospital because of short stature, reached the diagnosis of Muckle-Wells syndrome (MWS) due to a mutation in NLRP3 gene, which had not been reported so far (p.G328E, c.G983A). His mother and grandmother harbored the same mutation of NLRP3. We measured serum concentrations of cytokines in the proband assessed by flow-cytometric bead array. All of them had episodic skin eruptions with conjunctivitis, hearing loss, and arthralgia, but not periodic fever, cold-triggered episodes, and chronic aseptic meningitis. Only the proband had short stature. Canakinumab therapy led to a prompt relief of symptoms and normalized laboratory data in all patients. Audiograms demonstrated an improved hearing level in the proband, but not two others despite of the same mutation. All cytokines did not show any characteristic findings. Sensorineural hearing loss and itchless rash but not serum cytokine profile deserved attention to the diagnosis and treatment start of CAPS. The early intervention of IL-1β blockade may reduce the chance of complete deafness in patients with CAPS.

Keywords

CAPS G328E G983A Hearing loss IL-1β 

Notes

Acknowledgments

We thank the patients and their family for their cooperation.

Compliance with ethical standards

Disclosures

None.

Supplementary material

10067_2018_4331_Fig4_ESM.png (573 kb)
ESM 1

The results of genetic tests in the family with MWS. All the patients had a novel mutation in NLRP3 gene located on chromosome 1q44, p.G328E, c.G983A. (PNG 573 kb)

10067_2018_4331_MOESM1_ESM.tiff (2 mb)
High resolution image (TIFF 2028 kb)

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Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  • Yasunori Iida
    • 1
  • Hiroyuki Wakiguchi
    • 1
  • Fumiko Okazaki
    • 1
  • Tamaki Nakamura
    • 1
  • Hiroki Yasudo
    • 1
  • Makoto Kubo
    • 2
  • Kazuma Sugahara
    • 3
  • Hiroshi Yamashita
    • 3
  • Yutaka Suehiro
    • 4
  • Naoko Okayama
    • 5
  • Kunio Hashimoto
    • 6
  • Naoki Iwamoto
    • 7
  • Atsushi Kawakami
    • 7
  • Yoshiharu Aoki
    • 8
  • Hidetoshi Takada
    • 9
  • Shouichi Ohga
    • 1
    • 10
  • Shunji Hasegawa
    • 1
  1. 1.Department of PediatricsYamaguchi University Graduate School of MedicineYamaguchiJapan
  2. 2.Division of Cardiology, Department of Medicine and Clinical ScienceYamaguchi University Graduate School of MedicineUbeJapan
  3. 3.Department of OtolaryngologyYamaguchi University Graduate School of MedicineUbeJapan
  4. 4.Department of Oncology and Laboratory MedicineYamaguchi University Graduate School of MedicineUbeJapan
  5. 5.Division of LaboratoryYamaguchi University Graduate School of MedicineUbeJapan
  6. 6.Department of PediatricsNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  7. 7.Department of Immunology and RheumatologyNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  8. 8.Division of PediatricsNagato General HospitalNagatoJapan
  9. 9.Department of Child Health, Faculty of MedicineUniversity of TsukubaTsukubaJapan
  10. 10.Department of Pediatrics, Graduate School of Medical SciencesKyushu University Faculty of MedicineFukuokaJapan

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