Functional exercise capacity, strength, balance and motion reaction time in Barth syndrome

Brittany Hornby,Hilary J Vernon,Kimberley Carson,Rebecca Mcclellan,Tiffany Gooding,Lucy Buckley

doi:10.1186/s13023-019-1006-8

Abstract

BackgroundBarth syndrome (BTHS) is an X-linked disorder caused by defects in TAZ with key clinical features including cardiomyopathy, neutropenia and skeletal myopathy. In order to gain a better understanding of the range of clinical features, identify targets for monitoring, and increase knowledge of natural history of the disease, we conducted muscle strength testing, functional exercise capacity testing, physical activity assessment, balance assessment and motion reaction time testing in 33 affected individuals and 14 controls. We analyzed data points to provide a cross-sectional quantitative spectrum of disease characteristics. We also compared these data points to the matched data points collected two years prior to provide insight into effects of BTHS over time.ResultsIn comparison to controls, pediatric subjects with BTHS present with significantly impaired balance and motion reaction time while adult subjects with BTHS present with significantly impaired motion reaction time. In comparison to controls, subjects with BTHS presented with decreased functional exercise capacity (assessed via 6 MWT), knee extensor strength (both assessed via handheld dynamometry and five times sit-to-stand (5 TSTS)), and self-reported physical activity. Comparison of functional exercise capacity, knee extensor strength and self-reported physical activity from identical cohorts in 2014 and 2016 BTHS showed that the deficits in 6 MWT do not change significantly over the 2 year time span.ConclusionIn this comprehensive assessment of musculoskeletal parameters in a cross-section of individuals with BTHS, we uncovered deficits in motion reaction time and balance, which were previously not known to be abnormal in in BTHS. We also confirmed results of our previous study showing that pediatric and adult subjects with BTHS have decreased functional exercise capacity, knee extensor strength, and physical activity in comparison to controls, r, verifying the importance of including these measures as part of the regular clinical assessment in individuals with BTHS, as well as introducing 5 TSTS as an additional testing parameter. Perhaps most importantly, we demonstrated that 6 MWT results do not significantly vary in pediatric and adult cohorts with BTHS over a 2-year period, supporting this as a reliable quantitative measure of therapeutic outcomes in clinical studies and for clinical monitoring.

Highlights

Barth syndrome (BTHS) is an X-linked disorder caused by defects in TAZ with key clinical features including cardiomyopathy, neutropenia and skeletal myopathy
We expanded upon the musculoskeletal assessments performed in our previous study by including further functional testing in areas known to be affected by hip and knee flexor weakness [5, 6], and with high importance for quality of life and daily functioning (sit to stand testing (5 TSTS), quantitative balance assessment) and evaluated progression of musculoskeletal capacity in a subset of individuals over 2 years [2]
During our previous study we found that when normalized for body weight, pediatric subjects with BTHS presented with significantly greater knee extensor strength than adults with BTHS

Summary

Introduction

Barth syndrome (BTHS) is an X-linked disorder caused by defects in TAZ with key clinical features including cardiomyopathy, neutropenia and skeletal myopathy. Patients with BTHS present with exercise intolerance that is thought to be due to both cardiac impairment and decreased skeletal muscle oxygen utilization [4] Functional activities, such as ambulation, stair climbing, and transfers, require a combination of muscular strength, endurance, and balance. In our prior cross-sectional phenotyping study in with BTHS, we found that affected individuals had significantly impaired functional exercise capacity as measured by 6MWT, knee and hip flexor and extensor strength, and reduced daily activity. We expanded upon the musculoskeletal assessments performed in our previous study by including further functional testing in areas known to be affected by hip and knee flexor weakness [5, 6], and with high importance for quality of life and daily functioning (sit to stand testing (5 TSTS), quantitative balance assessment) and evaluated progression of musculoskeletal capacity in a subset of individuals over 2 years [2]. Functional exercise capacity, and balance will facilitate standardization of clinical assessments in BTHS, thereby allowing for improved ability to assess ongoing patient status and quantitatively evaluate response to treatment

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Results

Discussion

Conclusion