Development and validation of the modified-comprehensive Kumamoto Score: a multi-organ assessment tool for hereditary transthyretin amyloidosis

BACKGROUND: Disease-modifying therapies for hereditary transthyretin (ATTRv) amyloidosis necessitate sensitive, multi-organ assessment tools capturing early disease manifestations across heterogeneous phenotypes. We developed and validated the modified-comprehensive Kumamoto Score (mKS). METHODS: This prospective validation study enrolled 76 genetically confirmed ATTRv amyloidosis patients. The mKS comprises four organ-specific subscales: peripheral neuropathy (mKS-PN, 0-258), cardiomyopathy (mKS-CM, 0-195), eye (mKS-E, 0-60) and central nervous system (CNS) involvement (mKS-CNS, 0-45); total range 0-558. Construct validity was primarily assessed through Spearman's correlations with established clinical scores, objective biomarkers and patient-reported quality of life. RESULTS: = 0.155-0.381), confirming independent organ assessment. CONCLUSIONS: The mKS provides a validated comprehensive assessment tool for ATTRv amyloidosis with enhanced early-stage sensitivity and independent organ-specific subscales, addressing critical unmet needs in the era of disease-modifying therapies.