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Table 4 Overview of NP-C disease markers

From: Miglustat in Niemann-Pick disease type C patients: a review

Type Description and experience Subjective/objective Drawbacks Diagnosis Disease/treatment monitoring
General clinical impairment
NP-C disability scales • Categorical measures • Extensive use in clinical cohorts and case series Subjective • Variability of scales • Not very useful in EI pts X
Developmental delay / cognitive impairment • Subjective scales (MMSE, DDST) • Objective scales (WISCR/WAISR, Bayley-III) • Used in RCT, paediatric cohorts and case series/reports Subjective/objective • Limited disease specificity • Subjective measures X
SAI • General, practical scale • Used in key developmental clinical studies and case series Subjective • Limited disease specificity • Subjective measure X
Ocular motor assessments (VOG)
Saccadic eye movements (HSEM-α; HSEM-β, gain/latency) • Well-characterised measure • Used in key developmental clinical studies and cohort studies Objective X X
Swallowing assessments
Clinical observation • Multiple, varied assessments • Used in key developmental clinical studies Subjective • Time-consuming X
VFS • Direct measures standardised based on dysphagia scales • Used in multiple case series Objective • Not widely available X
Neuroimaging
MRI (volumetry) • Extensive published information • Used in cohort studies/case series Objective • Non-specificity • Only late-stage changes seen X
DTI (FA parameters) • Sensitive measures • Used in a clinical cohort and a case report Objective • Non-specificity • Requires specific expertise X
MRS (Cho/NAA ratio) • Sensitive measures • Used in clinical cohorts Objective • Non-specificity • Requires specific expertise X
PET (hypo/hyper-metabolism) • Dynamic, functional measures • Used in a case series Objective • Non-specificity • Requires specific expertise X
Neurotransmission
TMS (cortical plasticity) • Functional measure of neurological function • Used in a case series Objective • Non-specificity • Requires further validation X
Biomarkers
Filipin staining • Previous ‘gold standard’ marker based on patient skin biopsies • Extensively published use Objective • Labour-intensive: difficult to perform and interpret • Expensive • Not widely available X
Plasma ChT • Widely available LSD marker • Extensive published use in LSDs including NP-C Objective • Non-specificity • Null-ChT mutations • Lack of correlation with clinical manifestations X
CSF Cho/NAA ratio • Used in a cohort study/case series Objective • Limited published experience • Invasive assay procedure X
CSF calbindin • Highly specific marker • Used in a cohort study Objective • Invasive sampling procedure (spinal tap) X
Plasma oxysterols (c-triol, 7-keto) • Rapid, cost-effective markers • Widely used in diagnosis Objective • Lack of published data from disease monitoring X
Plasma bile acids • Rapid, cost-effective markers • Highly practical (useable in DBS) • Limited published experience Objective • Lack of published data from disease monitoring X
Lysosphingolipids (e.g., Lyso-SM-509) • Rapid, cost-effective markers • Highly practical (useable in DBS) • Limited published experience Objective • Lack of published data from disease monitoring X
  1. Bayley-III Bayley scales of infant development [50], ChT chitotriosidase, CSF cerebrospinal fluid, DBS dried blood spots, DDST Denver developmental screening test [49], DTI diffusion tensor imaging, EI early-infantile, FA fractional anisotropy, HSEM horizontal eye movements, MMSE mini-mental status evaluation [60], MRI magnetic resonance imaging, MRS magnetic resonance spectroscopy, PET positron emission tomography, SAI standard ambulation index, TMS transcranial magnetic stimulation, VFS videofluoroscopic studies, VOG video-oculography, WAISR Wechsler Adult Intelligence Test, WISCR Wechsler Intelligence Scale for Children [112]