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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]