Longitudinal analysis of anthropometric measures over 5 years in patients with Friedreich ataxia in the EFACTS natural history study

Abstract

Background: Friedreich ataxia is a rare neurodegenerative disorder caused by frataxin deficiency. Both underweight and overweight occur in mitochondrial disorders, each with adverse health outcomes. We investigated the longitudinal evolution of anthropometric abnormalities in Friedreich ataxia and the hypothesis that both weight loss and weight gain are associated with faster disease progression.

Methods: Participants were drawn from the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS). Age- and sex-specific BMI and height scores were calculated using the KIGGS-BMI percentiles for children. Height correction was applied for scoliosis. Longitudinal data were analysed using linear mixed effects models and incremental standard deviation scores and growth mixture models identified subclasses with varying BMI trajectories.

Results: Five hundred and forty-three adults and fifty-nine children were assessed for up to 5 years. In children, severe underweight (26%), underweight (7%), severe short stature (16%) and short stature (23%) were common. The corrected BMI percentile was stable in children, although 48% had negative incremental BMI scores over 1 year and 63% over 3 years versus 10%/year in a normal reference cohort. Overweight was common in adults (19%), with a slight increase in BMI over time. Longer GAA repeat size was linked to lower BMI in adults. Weight trajectory was not associated with ataxia progression in adults.

Conclusion: Significant anthropometric abnormalities were identified, with underweight and short stature prevalent in children and overweight in adults. These findings highlight the need for regular nutritional monitoring and interventions to manage underweight in children and promote healthy weight in adults.

Keywords: Friedreich ataxia; body height; body mass index; natural history; underweight.

FIGURE 1

Corrected BMI according to percentiles in male and female children at baseline. Legend: Each dot represents one child. BMI in children was defined as follows: severe underweight <3rd percentile, underweight <3–10th percentile, normal 10–90th percentile, overweight 90–97th percentile and obese >97th percentile. P3, 3rd percentile; P10, 10th percentile; P25, 25th percentile; P50, 50th percentile; P75, 75th percentile; P90, 90th percentile; P97, 97th percentile, BMI, body mass index.

FIGURE 2

Corrected height according to percentiles in male and female children at baseline. Each dot represents one child. Height in children was defined as follows: severe short stature <3rd percentile, short stature 3–10th percentile, normal 10–90th percentile, tall stature 90–97th percentile and very tall stature >97th percentile. P3, 3rd percentile; P10, 10th percentile; P25, 25th percentile; P50, 50th percentile; P75, 75th percentile; P90, 90th percentile; P97, 97th percentile.

FIGURE 3

Corrected BMI according over time in male and female adults. Mean corrected BMI over time in men and women. BMI: body mass index.

FIGURE 4

Corrected height percentile in male and female children over time. Mean corrected height percentile in male and female children.

FIGURE 5

Longitudinal evolution of SARA and ADL score according to corrected BMI category at baseline in adults. Linear mixed effect model with random intercept and random slope showing longitudinal evolution of SARA and ADL score with age in adults according to corrected BMI category. BMI category was defined as follows: Underweight: BMI < 18.5 (n = 40), normal: BMI 18.5–24.9 (n = 1623), overweight BMI > 25 (n = 136). ADL, activities of daily living; BMI, body mass index; SARA, Scale for the Assessment and Rating of Ataxia.