Body Mass Index and Height in the Friedreich Ataxia Clinical Outcome Measures Study

Maya Patel; Ashley McCormick; Jaclyn Tamaroff; Julia Dunn; Jonathan A Mitchell; Kimberly Y Lin; Jennifer Farmer; Christian Rummey; Susan L Perlman; Martin B Delatycki; George R Wilmot; Katherine D Mathews; Grace Yoon; Joseph Hoyle; Manuela Corti; S H Subramony; Theresa Zesiewicz; David Lynch; Shana E McCormack

doi:10.1212/NXG.0000000000000638

Body Mass Index and Height in the Friedreich Ataxia Clinical Outcome Measures Study

Neurol Genet. 2021 Nov 12;7(6):e638. doi: 10.1212/NXG.0000000000000638. eCollection 2021 Dec.

Authors

Maya Patel¹, Ashley McCormick¹, Jaclyn Tamaroff¹, Julia Dunn¹, Jonathan A Mitchell¹, Kimberly Y Lin¹, Jennifer Farmer¹, Christian Rummey¹, Susan L Perlman¹, Martin B Delatycki¹, George R Wilmot¹, Katherine D Mathews¹, Grace Yoon¹, Joseph Hoyle¹, Manuela Corti¹, S H Subramony¹, Theresa Zesiewicz¹, David Lynch¹, Shana E McCormack¹

Affiliation

¹ Division of Neurology (M.P., A.M.C., J.F., D.L.), Children's Hospital of Philadelphia; Department of Neurology (M.P., A.M.C., D.L.), Perelman School of Medicine at the University of Pennsylvania; Division of Endocrinology and Diabetes (J.T., J.D., S.E.M.), Children's Hospital of Philadelphia; Department of Pediatrics (J.A.M, K.Y.L., S.E.M.), Perelman School of Medicine at the University of Pennsylvania; Division of Gastroenterology (J.A.M.), Hepatology and Nutrition, Children's Hospital of Philadelphia; Division of Cardiology (K.Y.L), Children's Hospital of Philadelphia; Friedreich's Ataxia Research Alliance (J.F.); Clinical Data Science GmbH (C.R.), Basel, Switzerland; Department of Neurology (S.L.P), University of California Los Angeles; Murdoch Children's Research Institute (M.B.D.), Victoria, Australia; Department of Neurology (G.R.W), Emory University School of Medicine, Atlanta, Georgia; Department of Pediatrics (K.D.M.), University of Iowa Carver College of Medicine, Iowa; Divisions of Neurology (G.Y.) and Clinical and Metabolic Genetics, Department of Paediatrics, the Hospital for Sick Children, University of Toronto, Ontario, Canada; Department of Neurology (J.H.), Ohio State University College of Medicine, Columbus, Ohio; Department of Neurology (M.C., S.H.S.), University of Florida, College of Medicine, Gainesville, Florida; Department of Neurology (T.Z.), University of South Florida, Tampa, Florida.

Abstract

Background and objectives: Body mass index (BMI) and height are important indices of health. We tested the association between these outcomes and clinical characteristics in Friedreich ataxia (FRDA), a progressive neuromuscular disorder.

Methods: Participants (N = 961) were enrolled in a prospective natural history study (Friedreich Ataxia Clinical Outcome Measure Study). Age- and sex-specific BMI and height Z-scores were calculated using CDC 2000 references for participants younger than 18 years. For adults aged 18 years or older, height Z-scores were also calculated, and absolute BMI was reported. Univariate and multivariate linear regression analyses tested the associations between exposures, covariates, and BMI or height measured at the baseline visit. In children, the superimposition by translation and rotation analysis method was used to compare linear growth trajectories between FRDA and a healthy reference cohort, the Bone Mineral Density in Childhood Study (n = 1,535 used for analysis).

Results: Median age at the baseline was 20 years (IQR, 13-33 years); 49% (n = 475) were women. A substantial proportion of children (17%) were underweight (BMI-Z < fifth percentile), and female sex was associated with lower BMI-Z (β = -0.34, p < 0.05). In adults, older age was associated with higher BMI (β = 0.09, p < 0.05). Regarding height, in children, older age (β -0.06, p < 0.05) and worse modified Friedreich Ataxia Rating Scale (mFARS) scores (β = -1.05 for fourth quartile vs first quartile, p < 0.01) were associated with shorter stature. In girls, the magnitude of the pubertal growth spurt was less, and in boys, the pubertal growth spurt occurred later (p < 0.001 for both) than in a healthy reference cohort. In adults, in unadjusted analyses, both earlier age of FRDA symptom onset (=0.09, p < 0.05) and longer guanine-adenine-adenine repeat length (shorter of the 2 GAA repeats, β = -0.12, p < 0.01) were associated with shorter stature. Both adults and children with higher mFARS scores and/or who were nonambulatory were less likely to have height and weight measurements recorded at clinical visits.

Discussion: FRDA affects both weight gain and linear growth. These insights will inform assessments of affected individuals in both research and clinical settings.