Fig. 1.

Niemann-Pick disease type C laboratory diagnosis algorithm. Modified from: Patterson et al. [36, 47]. Abbreviations: GD: Gaucher disease; ASMD: acid sphingomyelinase deficiency; EM: electron microscopy; VUS: variant of unknown significance; MLPA: Multiplex Ligation-dependent Probe Amplification (evaluates copy number changes, allows detection of large deletions or false homozygous status with a deletion on the other allele); lysoSM: lysosphingomyelin. ^aElevated cholestane-triol or bile acid derivative and/or lysoSM-509, with normal or slightly elevated lysoSM. ^bCholestane-triol also elevated in ASMD, acid lipase deficiency, cerebrotendinous xanthomatosis, certain neonatal cholestasis conditions. All lysoSM analogues and bile acid derivative are elevated in ASMD. ^cI-cell disease (ML-II and -III) gives a false positive result (very different clinical features). ^dASMD can give a similar filipin pattern. ^eCheck allele segregation by parental study or other test