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Original Article
Biochemical and molecular characterisation of neurological Wilson disease
  1. Go Hun Seo1,
  2. Yoon-Myung Kim2,
  3. Seak Hee Oh1,
  4. Sun Ju Chung3,
  5. In Hee Choi4,
  6. Gu-Hwan Kim4,
  7. Mi-Sun Yum1,
  8. Jin-Ho Choi1,
  9. Kyung Mo Kim1,
  10. Tae-Sung Ko1,
  11. Beom Hee Lee1,4,
  12. Han-Wook Yoo1,4
  1. 1Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea
  2. 2Department of Pediatrics, Jeju National University School of Medicine, Jeju, Korea
  3. 3Department of Neurology, Asan Medical Center, Seoul, Korea
  4. 4Medical Genetics Center, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea
  1. Correspondence to Professor Beom Hee Lee and Prof. Han-Wook Yoo, Department of Pediatrics, University of Ulsan College of Medicine and Asan Medical Center, Seoul, 05505, Korea; bhlee{at}amc.seoul.kr, hwyoo{at}amc.seoul.kr

Abstract

Background To identify biochemical and genetic features that characterise neurological Wilson disease as a distinct disease subgroup.

Methods Detailed biochemical profiles and genotypic characteristics of neurological (86 patients) and hepatic subgroups (233 patients) from 368 unrelated Korean families were analysed.

Results Compared with patients in the hepatic subgroup, patients in the neurological subgroup had a later age at onset, a higher proportion with Kayser-Fleischer rings and higher serum creatinine levels, and a lower proportion with favourable outcome (62% vs 80%, P<0.016). At diagnosis, the neurological subgroup had lower serum ceruloplasmin (3.1±2.1 mg/dL vs 4.2±3.2 mg/dL, P<0.001), total copper (26.4±13.8 µg/dL vs 35.8±42.4 µg/dL, P=0.005), free copper (17.2±12.5 µg/dL vs 23.5±38.2 µg/dL, P=0.038) and urinary copper (280.9±162.9 µg/day vs 611.1±1124.2 µg/day, P<0.001) levels. Serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase and total bilirubin levels, as well as prothrombin time, were also lower in the neurological subgroup. Liver cirrhosis was more common but mostly compensated in the neurological subgroup. Frameshift, nonsense or splice-site ATP7B mutations and mutations in transduction or ATP hinge domains (2.4% vs 23.1%, P=0.006) were less common in the neurological subgroup.

Conclusion The neurological subgroup had distinct clinical, biochemical and genetic profiles. Further studies are required to identify the factors, with or without association with copper metabolism, underlying the neurological presentation for which treatment needs to be targeted to improve the clinical outcome of this subgroup.

  • wilson disease
  • neurological subgroup

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Footnotes

  • BHL and H-WY contributed equally.

  • Contributors GHS, BHL and H-WY contributed to designing the study. GHS drafted the manuscript and analysed the data. Y-MK, SHO, SJC, M-SY, T-SK, KMK, J-HC, BHL and H-WY were the treating paediatricians who conducted all clinical and neurological examinations. Genetic analysis was performed by G-HK, IHC and H-WY. H-WY and BHL revised the manuscript. All authors were involved in analysing and interpreting the data. All authors read and approved the final manuscript.

  • Funding This study was supported by a grant from the National Research Foundation of Korea, funded by the Ministry of Education, Science and Technology (NRF-2015R1D1A1A01058192 and NRF-2016M3A9B4915706).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval This study was approved by the institutional review board of the Asan Medical Center (2017-0551).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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