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 | – |