Key Health Measures, Height and Weight, Affected by FA at All Ages
Friedriech’s ataxia (FA) affects growth and weight in both adult and children, with the degree of differences from the general public in these key measures of health associated with disease severity, a study based on data from a large patient group reported.
While children showed a markedly higher prevalence of being underweight relative to a reference group in the U.S., the body mass index (BMI; a measure of body fat) of adult patients more closely resembled the general population.
Growth spurts in boys with FA were also seen to occur later than that of their healthy peers, while girls had a slower rate of growth.
Given the link between patients’ weight and height and disease severity, study investigators suggest those measure can help to inform patient assessments in both research and clinical settings.
The study, “Body Mass Index and Height in the Friedreich Ataxia Clinical Outcome Measures Study,” was published in the journal Neurology Genetics.
FA affects multiple systems, and common co-existing conditions include diabetes mellitus, scoliosis (a sideways curvature of the spine), and cardiomyopathy (heart muscle disease).
For a vast majority of patients, FA is caused by GAA nucleotide repeats in both copies of the frataxin (FXN) gene. Nucleotides are the DNA building blocks, with G being guanine and A adenine.
The frataxin protein is important for proper functioning of mitochondria, organelles that produce energy within cells. Metabolic problems caused by poorly working mitochondria in children with FA increase the risk of poor weight gain and growth.
“At the same time, mitochondrial disorders cause exercise intolerance and excess fatigue, leading to inactivity that increases the risk for weight gain and obesity, especially in affected adults,” the researchers wrote.
Understanding the association between weight gain and growth — important measures of overall health — and the clinical characteristics of FA can aid both in treating patients and researching this disease, the study noted.
A team led by researchers in the U.S. looked at the relationships linking demographic, genetic, and clinical factors with physical outcomes, such as height and BMI, in 961 patients with FA (median age of 20). Participants were from 12 different international sites and enrolled in a natural history study called FA-COMS (NCT03090789), which aims to expand the network of clinical research centers focused on FA, among other goals.
Overall, pediatric patients had longer trinucleotide repeats than adults, and an earlier median age of symptom onset (7 vs. 15 years). A higher number of GAA segments in the FXN gene corresponds to a younger age at onset, and more severe and rapidly progressing symptoms, the researchers noted.
Cardiomyopathy (64% vs. 41%) and scoliosis (83% vs. 71%) were significantly more common in children than in adult patients. In contrast, the pediatric incidence of diabetes was significantly lower than in adults, 1.5% vs. 7.0%.
“Cardiomyopathy that is severe and/or rapidly progressive has been associated with longer GAA expansions, and the difference in cardiomyopathy prevalence in our age-stratified cohorts [groups] is likely related to cohort-specific differences in GAA repeat length,” the researchers wrote.
By BMI, significantly more children were underweight than adult patients, 17% vs. 7%. Likewise, significantly fewer children were overweight or obese than adults, 8% vs. 33%.
Among the children, girls had a lower BMI z-score (an assessment of BMI relative to reference values) than did boys.
The investigators suggested that the lower BMI in girls, and its associated decrease in lean muscle mass, may explain the more rapid functional decline reported in women with FA than men.
Among adults, no differences were evident by sex. BMI was higher in older patients, those with later age of symptom onset or with shorter GAA repeat lengths, and in patients without scoliosis.
“One possible cause for excess weight gain with advancing age is that as individuals lose mobility over time, physical activity decreases, leading to excess weight gain. Moreover, excess weight can make physical activity even more challenging, leading to yet more inactivity,” the scientists wrote.
Researchers suggested that a higher BMI could also increase the risk of cardiometabolic concerns in FA patients.
A shorter height was evident in older children relative to reference values for their healthy peers than was seen for younger children. FA children with more severe disease were also shorter than those milder disease.
For adults, earlier age of symptom onset and longer nucleotide repeat lengths were linked to shorter height.
“In adults with [FA] … height was associated with genetic severity of disease, perhaps related to the cumulative effects of the condition,” the researchers wrote.
The investigators also noted that children with higher BMI scores were taller, whereas adults with higher BMI were shorter.
A growth curve model was then used to analyze children’s height post-puberty. Girls were slightly shorter and boys slightly taller than a reference group of similar sex and ancestry.
In boys with FA, the growth spurt associated with puberty occurred about a year later than in the reference group. Girls with FA after puberty showed a slower rate of growth than their matched peers.
Among this study’s limitations was a lack of height and/or weight measurements for about a quarter of the natural history study’s participants, its researchers noted, particularly those with more severe disease.
“In summary, we found that growth and weight gain are important indices of health in individuals with [FA],” the investigators wrote.
“Taken together, our findings indicate that careful measurements of weight and height in both clinical and research settings have the potential to yield additional relevant insights for health in individuals with [FA],” they added.
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