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Long-term efficacy of miglustat in paediatric patients with Niemann-Pick disease type C

  • Original Article
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Journal of Inherited Metabolic Disease

Abstract

Niemann-Pick disease type C (NP-C) is a rare inherited neurovisceral disease characterized by progressive neurological manifestations. Oral miglustat was first approved for the treatment of children and adults with NP-C in Europe in 2009. There are still relatively few published data on the long-term efficacy and safety of miglustat in patients with NP-C in clinical practice. We report the effects of up to 6 years of treatment with miglustat 100 mg t.i.d. in five children. Overall, 3/5 patients displayed progressive dysphagia before starting miglustat, and 4/5 showed marked cognitive and/or motor impairment. The mean age at treatment start was 11.6 years, and the median (range) duration of therapy so far is 4 (4.1 to 6.1) years. No treatment dose alterations were required, but therapy was interrupted for 1–3 months at least once in all patients due to supply issues. Swallowing function was stabilised during miglustat therapy, with no significant increase in Han dysphagia scale or aspiration-penetration index scores among four evaluable patients (p > 0.05). Scores on the mini-mental state examination indicated an improvement in cognitive function during the first 3–6 months of miglustat therapy, followed by stabilisation up to 5 years. Ambulatory function remained stable for at least the first 2 years of treatment in most patients, but there was a trend towards deterioration thereafter, possibly related to treatment interruptions. The safety/tolerability profile of miglustat was similar to previous clinical studies, although reports of gastrointestinal disturbances were rare. Overall, miglustat appeared to stabilise key parameters of neurological disease progression.

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Acknowledgements

The authors thank Dr. Michael Fietz at the Women and Children’s Hospital in North Adelaide, Australia, for performing fibroblast cholesterol esterification assays. Statistical analysis was provided by Pretium Pty Ltd, paid for by Actelion, Australia. Matthew Reilly, associated with InTouch Medical Ltd, provided medical writing assistance in the preparation of this manuscript, paid for by Actelion Pharmaceuticals Ltd.

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Authors and Affiliations

  1. Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan

    Y. H. Chien, N. C. Lee & W. L. Hwu

  2. Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan

    Y. H. Chien, N. C. Lee, A. C. Huang & W. L. Hwu

  3. Department of Radiology, National Taiwan University Hospital, Taipei, Taiwan

    S. F. Peng

  4. Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan

    C. C. Yang & L. K. Tsai

  5. Clinical Psychology Center/Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan

    S. C. Su & C. C. Tseng

  6. Department of Medical Genetics and Pediatrics, National Taiwan University Hospital, 8 Chung-Shan South Road, Taipei, 10041, Taiwan

    W. L. Hwu

Authors
  1. Y. H. Chien
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  2. S. F. Peng
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  3. C. C. Yang
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  4. N. C. Lee
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  5. L. K. Tsai
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  6. A. C. Huang
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  7. S. C. Su
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  8. C. C. Tseng
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  9. W. L. Hwu
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Corresponding author

Correspondence to W. L. Hwu.

Additional information

Communicated by: Ed Wraith

Appendix

Appendix

Table 3 Individual patient case histories (medical history before miglustat therapy)
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Chien, Y.H., Peng, S.F., Yang, C.C. et al. Long-term efficacy of miglustat in paediatric patients with Niemann-Pick disease type C. J Inherit Metab Dis 36, 129–137 (2013). https://doi.org/10.1007/s10545-012-9479-9

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  • DOI: https://doi.org/10.1007/s10545-012-9479-9

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