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Screening for Niemann-Pick Type C Disease in a Memory Clinic Cohort

  • Andreas Traschütz
  • Michael Thomas HenekaEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 44)

Abstract

Niemann-Pick type C disease (NPC) is a neurovisceral lysosomal storage disorder with a heterogeneous phenotype including ataxia, cognitive impairment, impairment of vertical saccades, and psychiatric symptoms, among many others. Based on clinical, genetic, and biomarker findings, recent guidelines put forward a screening for atypical and oligosymptomatic forms of NPC in clinical niches with an increased risk. Here, we report methods and results of a negative screening study in the niche of a memory clinic. We retrospectively and prospectively identified 83 patients with unclassified cognitive impairment (15 dementia, 46 mild cognitive impairment, and 22 progressive subjective cognitive decline) before 60 years of age (82 patients between 41 and 60 years). We explored the prevalence of clinical features compatible with NPC and measured plasma levels of chitotriosidase and cholestantriol. The NPC suspicion index indicated high probability for NPC in 3 and moderate probability in 16 patients. Prevalent (>5%) neurological and psychiatric features were depression, seizures, ataxia, dysarthria, and psychotic symptoms. Vertical gaze palsy without parkinsonism was observed in one patient. Cholestantriol levels were only abnormal in one patient. Chitotriosidase levels were susceptible to slight elevations that were reproducible in only two of five patients. Our study does not exclude NPC among memory clinic patients. Instead, we suggest conducting prospective screening studies in younger cohorts that include a focused neurological examination. Excluding minor cognitive impairment and discarding depression as an independent disease symptom probably further improve screening effectivity but may delay or miss therapeutic options in early or mild disease.

Keywords

Chitotriosidase Cholestantriol Cognition Niemann-Pick type C Screening Suspicion index 

References

  1. Bauer P, Balding DJ, Klunemann HH et al (2013) Genetic screening for Niemann-Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study. Hum Mol Genet 22(21):4349–4356CrossRefGoogle Scholar
  2. Bouzas L, Carlos Guinarte J, Carlos Tutor J (2003) Chitotriosidase activity in plasma and mononuclear and polymorphonuclear leukocyte populations. J Clin Lab Anal 17(6):271–275CrossRefGoogle Scholar
  3. Cupidi C, Frangipane F, Gallo M et al (2017) Role of Niemann-Pick type C disease mutations in dementia. J Alzheimers Dis 55(3):1249–1259CrossRefGoogle Scholar
  4. Geberhiwot T, Moro A, Dardis A et al (2018) Consensus clinical management guidelines for Niemann-Pick disease type C. Orphanet J Rare Dis 13(1):50CrossRefGoogle Scholar
  5. Hejl A, Hogh P, Waldemar G (2002) Potentially reversible conditions in 1000 consecutive memory clinic patients. J Neurol Neurosurg Psychiatry 73(4):390–394CrossRefGoogle Scholar
  6. Hendriksz CJ, Pineda M, Fahey M et al (2015) The Niemann-Pick disease type C suspicion index: development of a new tool to aid diagnosis. J Rare Disord Diagn Ther 1:11Google Scholar
  7. Jiang X, Sidhu R, Porter FD et al (2011) A sensitive and specific LC-MS/MS method for rapid diagnosis of Niemann-Pick C1 disease from human plasma. J Lipid Res 52(7):1435–1445CrossRefGoogle Scholar
  8. Klarner B, Klünemann H, Lürding R, Aslanidis C, Rupprecht R (2007) Neuropsychological profile of adult patients with Niemann-Pick C1 (NPC1) mutations. J Inherit Metab Dis 30(1):60–67CrossRefGoogle Scholar
  9. Knapskog A-B, Barca ML, Engedal K (2014) Prevalence of depression among memory clinic patients as measured by the Cornell Scale of Depression in dementia. Aging Ment Health 18(5):579–587CrossRefGoogle Scholar
  10. Oguro H, Okada K, Suyama N, Yamashita K, Yamaguchi S, Kobayashi S (2004) Decline of vertical gaze and convergence with aging. Gerontology 50(3):177–181CrossRefGoogle Scholar
  11. Patterson MC, Hendriksz CJ, Walterfang M et al (2012) Recommendations for the diagnosis and management of Niemann-Pick disease type C: an update. Mol Genet Metab 106(3):330–344CrossRefGoogle Scholar
  12. Patterson MC, Mengel E, Wijburg FA et al (2013) Disease and patient characteristics in NP-C patients: findings from an international disease registry. Orphanet J Rare Dis 8(1):12CrossRefGoogle Scholar
  13. Patterson MC, Clayton P, Gissen P et al (2017) Recommendations for the detection and diagnosis of Niemann-Pick disease type C an update. Neurol Clin Pract 7:499–511.  https://doi.org/10.1212/CPJ.0000000000000399 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Reunert J, Lotz-Havla A, Polo G et al (2015) Niemann-Pick type C-2 disease: identification by analysis of plasma cholestane-3β, 5α, 6β-triol and further insight into the clinical phenotype. JIMD Rep 23:17–26CrossRefGoogle Scholar
  15. Reunert J, Fobker M, Kannenberg F et al (2016) Rapid diagnosis of 83 patients with Niemann-Pick type C disease and related cholesterol transport disorders by cholestantriol screening. EBioMedicine 4:170–175CrossRefGoogle Scholar
  16. Richard E, Reitz C, Honig LH et al (2013) Late-life depression, mild cognitive impairment, and dementia. JAMA Neurol 70(3):383–389CrossRefGoogle Scholar
  17. Rossor MN, Fox NC, Mummery CJ, Schott JM, Warren JD (2010) The diagnosis of young-onset dementia. Lancet Neurol 9(8):793–806CrossRefGoogle Scholar
  18. Salsano E, Umeh C, Rufa A, Pareyson D, Zee DS (2012) Vertical supranuclear gaze palsy in Niemann-Pick type C disease. Neurol Sci 33(6):1225–1232CrossRefGoogle Scholar
  19. Schicks J, Muller Vom Hagen J, Bauer P et al (2013) Niemann-Pick type C is frequent in adult ataxia with cognitive decline and vertical gaze palsy. Neurology 80(12):1169–1170CrossRefGoogle Scholar
  20. Sevin M, Lesca G, Baumann N et al (2007) The adult form of Niemann-Pick disease type C. Brain 130(Pt 1):120–133PubMedGoogle Scholar
  21. Vanier MT (2010) Niemann-Pick disease type C. Orphanet J Rare Dis 5:16CrossRefGoogle Scholar
  22. Vanier MT, Gissen P, Bauer P et al (2016) Diagnostic tests for Niemann-Pick disease type C (NP-C): a critical review. Mol Genet Metab 118(4):244–254CrossRefGoogle Scholar
  23. Wassif CA, Cross JL, Iben J et al (2016) High incidence of unrecognized visceral/neurological late-onset Niemann-Pick disease, type C1, predicted by analysis of massively parallel sequencing data sets. Genet Med 18(1):41–48CrossRefGoogle Scholar
  24. Wijburg FA, Sedel F, Pineda M et al (2012) Development of a suspicion index to aid diagnosis of Niemann-Pick disease type C. Neurology 78(20):1560–1567CrossRefGoogle Scholar
  25. Żurawska-Płaksej E, Knapik-Kordecka M, Rorbach-Dolata A, Piwowar A (2016) Increased chitotriosidase activity in plasma of patients with type 2 diabetes. Arch Med Sci 12(5):977CrossRefGoogle Scholar

Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  1. 1.Department of NeurologyUniversity Hospital BonnBonnGermany
  2. 2.Department of Neurodegenerative Diseases and Gerontopsychiatry/NeurologyUniversity Hospital BonnBonnGermany
  3. 3.German Center for Neurodegenerative Diseases (DZNE)BonnGermany

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