Role of novel laboratory techniques in Niemann-Pick type C disease diagnostics

Czech version

Authors: M. Hřebíček ¹; H. Jahnová ²; L. Dvořáková ^1,2; F. Majer ¹; D. Mušálková ¹; J. Ledvinová ¹; L. Kuchař ¹
Authors‘ workplace: Laboratoř pro studium vzácných nemocí, Klinika dětského a dorostového, lékařství 1. LF UK a VFN v Praze ¹; Klinika dětského a dorostového lékařství 1. LF UK a VFN v Praze ²
Published in: Cesk Slov Neurol N 2020; 83/116(3): 263-268
Category: Review Article
doi: https://doi.org/10.14735/amcsnn2020263

Overview

This review provides a summary of current approaches to Niemann-Pick disease type C (NP-C) diag-nostics with an emphasis on novel laboratory techniques. NP-C is a severe autosomal recessive neurovisceral disorder and the recent availability of disease-modifying therapies increases the importance of its timely diagnosis. The hereditary deficiency of cholesterol transporter proteins (NPC1 or NPC2) in NP-C leads to abnormal intracellular lipid trafficking. Clinical suspicion for NP-C has to be confirmed by biochemical and/or molecular genetic methods. Novel biomarkers in serum or plasma and advanced sequencing techniques now have a prominent role in NP-C diagnostics. In a subset of patients, it is necessary to use several complementary techniques for confirmation of NP-C diagnosis, including advanced biochemical and cellular assays discussed in the paper. These methods therefore have to be available in a specialized laboratory.Niemann-Pickova choroba typu C –⁠ diagnostika –⁠ intracelulární transport cholesterolu –⁠ biomarkery –⁠ lyzosfi ngolipidy –⁠ oxysteroly –⁠ fi lipinový test

Keywords:

biomarkers – oxysterols – Niemann-Pick disease type C – diagnostics – intracellular cholesterol traffi cking – lysosphingolipids – filipin test

Sources

1. Vanier MT. Niemann-Pick disease type C. Orphanet J Rare Dis 2010; 5 : 16. doi: 10.1186/1750-1172-5-16.

2. Jahnová H, Dvořáková L, Hůlková H et al. Diagnostika a možnosti léčby Niemann-Pickovy choroby typ C. Cesk Slov Neurol N 2012; 75/108 (3): 303–308.

3. Nadjar Y, Hütter-Moncada AL, Latour P et al. Adult Niemann-Pick disease type C in France: clinical phenotypes and long-term miglustat treatment effect. Orphanet J Rare Dis 2018; 13 (1): 175. doi: 10.1186/s13023-018-0913-4.

4. Mengel E, Klünemann HH, Lourenço CM et al. Niemann-Pick disease type C symptomatology: an expert-based clinical description. Orphanet J Rare Dis 2013; 8 : 166. doi: 10.1186/1750-1172-8-166.

5. Wijburg FA, Sedel F, Pineda M et al. Development of a suspicion index to aid diagnosis of Niemann-Pick disease type C. Neurology 2012; 78 (20): 1560–1567. doi: 10.1212/WNL.0b013e3182563b82.

6. Pineda M, Mengel E, Jahnová H et al. A Suspicion Index to aid screening of early-onset Niemann-Pick disease Type C (NP-C). BMC Pediatr 2016; 16 : 107. doi: 10.1186/s12887-016-0641-7.

7. Patterson MC, Garver WS, Giugliani R et al. Long-term survival outcomes of patients with Niemann-Pick disease type C receiving miglustat treatment: a large retrospective observational study. J Inherit Metab Dis 2020 Apr 23 [Online ahead of print]. doi: 10.1002/jimd.12245.

8. Farmer CA, Thurm A, Farhat N et al. Long-term neuropsychological outcomes from an open-label phase I/IIa trial of 2-hydroxypropyl-b-cyclodextrins (VTS-270) in Niemann-Pick disease, type C1. CNS Drugs 2019; 33 (7): 677–683. doi: 10.1007/s40263-019-00642-2.

9. Kirkegaard T, Gray J, Priestman DA et al. Heat shock protein-based therapy as a potential candidate for treating the sphingolipidoses. Sci Transl Med 2016; 8 (355): 355ra118. doi: 10.1126/scitranslmed.aad9823.

10. Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science 1986; 232 (4746): 34–47. doi: 10.1126/science.3513311.

11. Pfeffer SR. NPC intracellular cholesterol transporter 1 (NPC1) -mediated cholesterol export from lysosomes. J Biol Chem 2019; 294 (5): 1706–1709. doi: 10.1074/jbc.TM118.004165.

12. Ikonen E. Mechanisms of cellular cholesterol compartmentalization: recent insights. Curr Opin Cell Biol 2018; 53 : 77–83. doi: 10.1016/j.ceb.2018.06.002.

13. Vanier MT. Complex lipid trafficking in Niemann-Pick disease type C. J Inherit Metab Dis 2015; 38 (1): 187–199. doi: 10.1007/s10545-014-9794-4.

14. Porter FD, Scherrer DE, Lanier MH et al. Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease. Sci Transl Med 2010; 2 (56): 56ra81. doi: 10.1126/scitranslmed.3001417.

15. Richards S, Aziz N, Bale S et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17 (5): 405–423. doi: 10.1038/gim.2015.30.

16. Geberhiwot T, Moro A, Dardis A et al. Consensus clinical management guidelines for Niemann-Pick disease type C. Orphanet J Rare Dis 2018; 13 (1): 50. doi: 10.1186/s13023-018-0785-7.

17. Vanier MT, Latour P. Laboratory diagnosis of Niemann-Pick disease type C: the filipin staining test. Methods Cell Biol 2015; 126 : 357–375. doi: 10.1016/bs.mcb.2014.10.028.

18. Tängemo C, Weber D, Theiss S et al. Niemann--Pick Type C disease: characterizing lipid levels in patients with variant lysosomal cholesterol storage. J Lipid Res 2011; 52 (4): 813–825. doi: 10.1194/jlr.P013524.

19. Vanier MT, Wenger DA, Comly ME et al. Niemann--Pick disease group C: clinical variability and diagnosis based on defective cholesterol esterification: a collaborative study on 70 patients. Clin Genet 1988; 33 (5): 331–348. doi: 10.1111/j.1399-0004.1988.tb03460.x.

20. Vanier MT, Gissen P, Bauer P et al. Diagnostic tests for Niemann-Pick disease type C (NP-C): A critical review. Mol Genet Metab 2016; 118 (4): 244–254. doi: 10.1016/j.ymgme.2016.06.004.

21. Piras I, Melis A, Ghiani ME et al. Human CHIT1 gene distribution: new data from Mediterranean and European populations. J Hum Genet 2006; 52 (2): 110–116. doi: 10.1007/s10038-006-0086-1.

22. Michelakakis H, Dimitriou E, Labadaridis I. The expanding spectrum of disorders with elevated plasma chitotriosidase activity: an update. J Inherit Metab Dis 2004; 27 (5): 705–706. doi: 10.1023/b: boli.0000043025.17721.fc.

23. Vanier MT, Gissen P, Bauer P et al. Diagnostic tests for Niemann-Pick disease type C (NP-C): A critical review. Mol Genet Metab 2016; 118 (4): 244–254. doi: 10.1016/j.ymgme.2016.06.004.

24. Sidhu R, Mondjinou Y, Qian M et al. N-acyl-O-phosphocholineserines: structures of a novel class of lipids that are biomarkers for Niemann-Pick C1 disease. J Lipid Res 2019; 60 (8): 1410–1424. doi: 10.1194/jlr.RA119000157.

25. Kuchar L, Sikora J, Gulinello ME et al. Quantitation of plasmatic lysosphingomyelin and lysosphingomyelin-509 for differential screening of Niemann-Pick A/B and C diseases. Anal Biochem 2017; 525 : 73–77. doi: 10.1016/j.ab.2017.02.019.

26. Lipiński P, Kuchar L, Zakharova EY et al. Chronic visceral acid sphingomyelinase deficiency (Niemann-Pick disease type B) in 16 Polish patients: long-term follow-up. Orphanet J Rare Dis 2019; 14 (1): 55. doi: 10.1186/s13023-019-1029-1.

27. Jiang X, Sidhu R, Mydock-McGrane L et al. Development of a bile acid-based newborn screen for Niemann-Pick disease type C. Sci Transl Med 2016; 8 (337): 337ra63. doi: 10.1126/scitranslmed.aaf2326.

28. Jiang X, Sidhu R, Orsini JJ et al. Diagnosis of niemann--pick C1 by measurement of bile acid biomarkers in archived newborn dried blood spots. Mol Genet Metab 2019; 126 (2): 183–187. doi: 10.1016/j.ymgme.2018.08.007.

29. Elleder M. Diagnosis of Niemann–Pick type C (NPC) –⁠ decisions at the cell level. Pathologist’s report. Mol Genet Metab 2010; 99 (1): 98. doi: 10.1016/j.ymgme.2009.09.011.

30. Wraith JE, Baumgartner MR, Bembi B et al. Recommendations on the diagnosis and management of Niemann-Pick disease type C. Mol Genet Metab 2009; 98 (1–2): 152–165. doi: 10.1016/j.ymgme.2009.06.008.

31. Kelly DA, Portmann B, Mowat AP et al. Niemann-Pick disease type C: diagnosis and outcome in children, with particular reference to liver disease. J Pediatr 1993; 123 (2): 242–247. doi: 10.1016/S0022-3476 (05) 81695-6.

32. Hendriksz CJ, Anheim M, Bauer P et al. The hidden Niemann-Pick type C patient: clinical niches for a rare inherited metabolic disease. Curr Med Res Opin 2017; 33 (5): 877–890. doi: 10.1080/03007995.2017.1294054.

33. Bauer P, Balding DJ, Klünemann HH et al. Ge-netic screening for Niemann-Pick disease type Cin adults with neurological and psychiatric symptoms: findings from the ZOOM study. Hum Mol Genet 2013; 22 (21): 4349–4356. doi: 10.1093/hmg/ddt284.

34. Wassif CA, Cross JL, Iben J et al. High incidence of unrecognized visceral/neurological late-onset Niemann--Pick disease, type C1, predicted by analysis of massively parallel sequencing data sets. Genet Med 2016; 18 (1): 41–48. doi: 10.1038/gim.2015.25.

35. Sobrido MJ, Bauer P, de Koning T et al. Recommendations for patient screening in ultra-rare inherited metabolic diseases: what have we learned from Niemann--Pick disease type C? Orphanet J Rare Dis 2019; 14 (1): 20. doi: 10.1186/s13023-018-0985-1.

36. Společnost lékařské genetiky a genomiky České lékařské společnosti Jana Evangelisty Purkyně. Databáze genetických pracovišť. Dostupné z URL: https: //slg.cz/pracoviste/.