Figure 3

Laboratory diagnosis algorithm. Footnote: This algorithm is as proposed in Wraith et al. Mol Genet Metab 2009, 98:152-165 [27] *Sphingomyelinase deficiency (including late-onset type A) may give a dubious filipin pattern, with normal kinetics of LDL-induced cholesteryl ester formation ** False positive: I-cell disease (but very different clinical features) ***Heterozygotes may show a pattern (filipin staining and kinetics of LDL-induced cholesteryl ester formation) similar to that in "variant" patients ****In many countries, NPC1 p.P1007A or different missense mutations on codon 992 constitute the most frequent "variant" mutations Genetic studies can also be undertaken if clinical symptoms are very suggestive of a diagnosis of NP-C, even with negative results from filipin testing.