Skip to main content
Log in

Treatment of a child diagnosed with Niemann–Pick disease type C with miglustat: A case report in Brazil

  • Short Report
  • Published:
Journal of Inherited Metabolic Disease


Niemann–Pick disease type C (NPC) is an autosomal recessive neurovisceral lysosomal lipid storage disorder that leads to variable symptoms that include cognitive decline, ataxia, dystonia, cataplexy, vertical supranuclear gaze palsy, and seizures. Currently, there is no specific treatment for NPC other than palliative care. Substrate reduction therapy represents a potential strategy for treating this debilitating neurodegenerative disorder. Miglustat (Zavesca) is a reversible inhibitor of the enzyme glucosylceramide synthase, which catalyses the first step in the biosynthesis of most glycosphingolipids. Miglustat has pharmacokinetic properties that allow it to cross the blood–brain barrier, thus making it a potential therapeutic agent for treating neurological symptoms in NPC patients. We present here a case report of a Brazilian child treated with miglustat. Before treatment, the patient presented with difficulties walking and swallowing, slurred speech, moderate cognitive impairments, ataxia, ptosis, and vertical supranuclear ophthalmoplegia. On a disability scale, the patient obtained a score of 15 before treatment and 8 after treatment. Following 12 months of treatment, the patient remained stable with improvements in speech, ptosis, ophthalmoplegia, ataxia, hypotonia and seizures. The Child Behavior Checklist (CBCL) was used to assess psychopathological, behavioural and social problems before and after treatment. The CBCL showed that indices for depression, affective and attention problems were all in the normal range following treatment. Thus, for this individual miglustat was an effective, well-tolerated and efficacious medication for treatment of NPC symptoms. Follow-up maintenance studies are vital to establish whether both the efficacy and safety of miglustat persist with time.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others



Child behavior checklist


Magnetic resonance imaging


Niemann–Pick disease type C


every day


three times a day


  • Achenbach TM (1991) Manual for the Child Behavior Checklist/4-18 and 1991 Profile. Burlington, VT: University of Vermont Department of Psychiatry.

    Google Scholar 

  • Achenbach TM, Ruffle TM (2000) The Child Behavior Checklist and related forms for assessing behavioral/emotional problems and competencies. Pediatr Rev 21: 265–271. doi:10.1542/pir.21-8-265.

    Article  PubMed  CAS  Google Scholar 

  • Chien YH, Lee NC, Tsai LK, et al (2007) Treatment of Niemann–Pick disease type C in two children with miglustat: initial responses and maintenance of effects over 1 year. J Inherit Metab Dis 30: 826–833. doi:10.1007/s10545-007-0630-y.

    Article  PubMed  Google Scholar 

  • Erickson RP, Garver WS, Camargo F, et al (2000) Pharmacological and genetic modifications of somatic cholesterol do not substantially alter the course of CNS disease in Niemann–Pick C mice. J Inherit Metab Dis 23: 54–62. doi:10.1023/A:1005650930330.

    Article  PubMed  CAS  Google Scholar 

  • Imrie J, Dasgupta S, Besley GT, et al (2007) The natural history of Niemann–Pick disease type C in the UK. J Inherit Metab Dis 30: 51–59. doi:10.1007/s10545-006-0384-7.

    Article  PubMed  CAS  Google Scholar 

  • Iturriaga C, Pineda M, Fernandez-Valero EM, et al (2006) Niemann–Pick C disease in Spain: clinical spectrum and development of a disability scale. J Neurol Sci 249: 1–6. doi:10.1016/j.jns.2006.05.054.

    Article  PubMed  CAS  Google Scholar 

  • Lachmann RH, te Vruchte D, Lloyd-Evans E, et al (2004) Treatment with miglustat reverses the lipid-trafficking defect in Niemann–Pick disease type C. Neurobiol Dis 16: 654–658. doi:10.1016/j.nbd.2004.05.002.

    Article  PubMed  CAS  Google Scholar 

  • Paciorkowski AR, Westwell M, Ounpuu S, et al (2008) Motion analysis of a child with Niemann–Pick disease type C treated with miglustat. Mov Disord 23: 124–128. doi:10.1002/mds.21779.

    Article  PubMed  Google Scholar 

  • Patterson MC, Di Bisceglie AM, Higgins JJ, et al (1993) The effect of cholesterol-lowering agents on hepatic and plasma cholesterol in Niemann–Pick disease type C. Neurology 43: 61–64.

    PubMed  CAS  Google Scholar 

  • Patterson MC, Vanier MT, Suzuki K, et al (2001) Niemann-Pick disease type C: a lipid trafficking disorder. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc. eds. The Metabolic and Molecular Bases of Inherited Disease, 8th Edn. New York: McGraw-Hill, 3611–3633.

  • Patterson MC, Vecchio D, Prady H, et al (2007) Miglustat for treatment of Niemann–Pick C disease: a randomised controlled study. Lancet Neurol 6: 765–772. doi:10.1016/S1474-4422(07)70194-1.

    Article  PubMed  CAS  Google Scholar 

  • Saunier B, Kilker RD Jr, Tkacz JS, et al (1982) Inhibition of N-linked complex oligosaccharide formation by 1-deoxynojirimycin, an inhibitor of processing glucosidases. J Biol Chem 257: 14155–14161.

    PubMed  CAS  Google Scholar 

  • Sevin M, Lesca G, Baumann N, et al (2007) The adult form of Niemann–Pick disease type C. Brain 130(Pt 1): 120–133. doi:10.1093/brain/awl260.

    PubMed  Google Scholar 

  • Treiber A, Morand O, Clozel M (2007) The pharmacokinetics and tissue distribution of the glucosylceramide synthase inhibitor miglustat in the rat. Xenobiotica 37: 298–314. doi:10.1080/00498250601094543.

    Article  PubMed  CAS  Google Scholar 

  • Vanier MT, Millat G (2003) Niemann–Pick disease type C. Clin Genet 64: 269–281. doi:10.1034/j.1399-0004.2003.00147.x.

    Article  PubMed  CAS  Google Scholar 

  • Wadzinski J, Franks R, Roane D, et al (2007) Valproate-associated hyperammonemic encephalopathy. J Am Board Fam Med 20: 499–502. doi:10.3122/jabfm.2007.05.070062.

    Article  PubMed  Google Scholar 

  • Walkley SU, Suzuki K (2004) Consequences of NPC1 and NPC2 loss of function in mammalian neurons. Biochim Biophys Acta 1685: 48–62.

    PubMed  CAS  Google Scholar 

  • Zervas M, Somers KL, Thrall MA, et al (2001) Critical role for glycosphingolipids in Niemann–Pick disease type C. Curr Biol 11: 1283–1287. doi:10.1016/S0960-9822(01)00396-7.

    Article  PubMed  CAS  Google Scholar 

Download references


We thank Dr Cameron B. Gundersen for critical reading of the manuscript, and Jaqueline Kolberg for assistance with the illustrations. M. L. C. gratefully acknowledges support from Mr Norbert Gehr. We also thank the patient’s family for allowing this publication.

Author information

Authors and Affiliations


Corresponding author

Correspondence to M. L. Cordeiro.

Additional information

Communicating editor: Guy Besley

Competing interests: None declared

Rights and permissions

Reprints and permissions

About this article

Cite this article

Santos, M.L.F., Raskin, S., Telles, D.S. et al. Treatment of a child diagnosed with Niemann–Pick disease type C with miglustat: A case report in Brazil. J Inherit Metab Dis 31 (Suppl 2), 357–361 (2008).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: