ABSTRACT: This study proposes a reliable computer-aided framework to identify gait fluctuations associated with a wide range of degenerative neuromuscular disease (DNDs) and health conditions. Investigated DNDs included amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Huntington's disease (HD). We further performed a statistical and classification comparison elucidating the discriminative capability of different gait signals, including vertical ground reaction force (VGRF), stride duration, stance duration, and swing duration. Feature representation of these gait signals was based on statistical amplitude quantification using the root mean square (RMS), variance, kurtosis, and skewness metrics. We investigated various decision tree (DT) based ensemble methods such as bagging, adaptive boosting (AdaBoost), random under-sampling boosting (RUSBoost), and random subspace to tackle the challenge of multi-class classification. Experimental results showed that AdaBoost ensembling provided a 6.49%, 0.78%, 2.31%, and 2.72% prediction rate improvement for the VGRF, stride, stance, and swing signals, respectively. The proposed approach achieved the highest classification accuracy of 99.17%, sensitivity of 98.23%, and specificity of 99.43%, using the VGRF-based features and the adaptive boosting classification model. This work demonstrates the effective capability of using simple gait fluctuation analysis and machine learning approaches to detect DNDs. Computer-aided analysis of gait fluctuations provides a promising advent to enhance clinical diagnosis of DNDs.