Association of Body Mass Index With Disease Progression in Children With Charcot-Marie-Tooth Disease

Objective: The study aim was to evaluate the impact of body mass index (BMI) on disease progression over 2-years in children with Charcot-Marie-Tooth disease (CMT). Methods: BMI was classified in 242 participants 3-20 years with CMT enrolled in the Inherited Neuropathy Consortium, using the International Obesity Task Force (based on adult BMI values, kg/m²). Groups were categorised as severely underweight (BMI<17kg/m²), underweight (BMI≥17kg/m² to <18.5kg/m²), healthy weight (BMI≥18.5kg/m² to <25kg/m²), overweight (BMI≥25 kg/m² to <30 kg/m²) and obese (BMI≥30kg/m²). Disease severity was assessed using the CMT Pediatric Scale (CMTPedS), a clinical outcome assessment of disability (0-44 points, mild-severe).

Results: At baseline, compared to being healthy weight (mean CMTPedS 15.48, SD 9.22), children who were severely underweight (mean CMTPedS difference 9.03, 95%CI 0.94-17.12; p=0.02,), underweight (mean CMTPedS difference 5.97, 95%CI 0.62-11.31; p=0.02), or obese (mean CMTPedS difference 7.96, 95%CI 1.03-14.88; p=0.015) exhibited greater disability. At 2-years, compared to being healthy weight (mean CMTPedS 17.53, SD 9.41), children who were severely underweight exhibited greater disability (mean CMTPedS difference 9.27, 95%CI 0.90-17.64; p=0.02). Over the 2-year periods, mean CMTPedS for the whole sample deteriorated by 1.72 points (95%CI 1.09-2.38; p<0.001), with severely underweight children progressing at the fastest rate (mean CMTPedS change of 2.3, 95%CI 1.53 – 6.13; p=0.21). In children who did not change BMI categories over 2-years (69% of sample), CMTPedS scores deteriorated faster in those who were severely underweight (mean CMTPedS change 6.40 points 95%CI 2.42 -10.38; p=0.01) than those of a healthy weight (mean CMTPedS change 1.79 points 95%CI 0.93 - 2.69; p<0.001). For children who changed BMI categories (31% of sample), CMTPedS scores deteriorated faster in children who became overweight/obese (mean CMTPedS change 2.76 points 95%CI 0.11 - 5.41; p=0.031).

Conclusion: Children with CMT who severely underweight, underweight, or obese exhibited greater disability at baseline. Over the 2-year period in those whose BMI remained stable, severely underweight children deteriorated at the fastest rate. For children who changed BMI categories over the 2 years, CMTPedS scores deteriorated faster in children who became overweight/obese. Interventions that maintain or improve BMI towards a healthy weight may reduce disability in children with CMT.