Niemann-Pick disease type C laboratory diagnosis algorithm

(Modified from: Patterson MC, Hendriksz CJ, Walterfang M, et al. Recommendations for the diagnosis and management of Niemann-Pick disease type C: an update. Mol Genet Metab 2012;106(3):330-44. And Patterson MC, Clayton P, Gissen P, et al. Recommendations for the detection and diagnosis of Niemann-Pick disease type C. Neurol Clin Pract 2017;7(6):499-511.) Abbreviations: GD: Gaucher disease; ASM: acid sphingomyelinase; EM: electron microscopy; MLPA: Multiplex Ligation-dependent Probe Amplification. This technique evaluates copy number changes and has allowed detection of large deletions, so far only in the NPC1 gene. It has also been useful to detect a false homozygous status with a deletion on the other allele. (a) New test under clinical development, see text; (b) I-cell disease (ML-II and –III) gives a false positive result (but very different clinical features); (c) ASM deficiency can give a similar filipin pattern; (d) not certainly pathogenic; (e) DNA is usually needed to study the effect of splice mutations; (f) check allele segregation by parental study.