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Published on: January 12, 2019
Gross Motor Function in Pediatric Onset TUBB4A-Related Leukodystrophy: GMFM-88 Performance and Validation of GMFC-MLD
Francesco Gavazzi1, Virali Patel1, Brittany Charsar1
1Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Abstract:
TUBB4A pathogenic variants are associated with a spectrum of neurologic impairments including movement disorders and leukodystrophy. With the development of targeted therapies, there is an urgent unmet need for validated tools to measure mobility impairment. Our aim is to explore gross motor function in a pediatric-onset TUBB4A-related leukodystrophy cohort with existing gross motor outcome tools. Gross Motor Function Measure-88 (GMFM-88), Gross Motor Function Classification System (GMFCS-ER), and Gross Motor Function Classification-Metachromatic Leukodystrophy (GMFC-MLD) were selected through face validity. Subjects with a confirmed clinical and molecular diagnosis of TUBB4A-related leukodystrophy were enrolled. Participants' sex, age, genotype, and age at disease onset were collected, together with GMFM-88 and concurrent GMFCS-ER and GMFC-MLD. Performances on each measure were compared. GMFM-88 floor effect was defined as total score below 20%. A total of 35 subjects participated. Median performance by GMFM-88 was 16.24% (range 0-97.31), with 42.9% (n = 15) of individuals performing above the floor. GMFM-88 Dimension A (Lying and Rolling) was the best-performing dimension in the GMFM-88 (n = 29 above the floor). All levels of the Classification Scales were represented, with the exception of the GMFC-MLD level 0. Evaluation by GMFM-88 was strongly correlated with the Classification Scales (Spearman correlations: GMFCS-ER:GMFM-88 r = 0.90; GMFC-MLD:GMFM-88 r = 0.88; GMFCS-ER:GMFC-MLD: r = 0.92). Despite overall observation of a floor effect, the GMFM-88 is able to accurately capture the performance of individuals with attenuated phenotypes. GMFM-88 Dimension A shows no floor effect. GMFC-MLD shows a strong correlation with GMFCS-ER and GMFM-88, supporting its use as an age-independent functional score in TUBB4A-related leukodystrophy.
Insights
This study evaluated mobility in children with TUBB4A-related leukodystrophy using the Gross Motor Function Measure-88 (GMFM-88). Results show GMFM-88 can assess function, especially Dimension A, despite a general floor effect in the cohort.
Area of Science:
- Neurology
- Genetics
- Pediatrics
Background:
- Pathogenic variants in the TUBB4A gene cause a range of neurological issues, including movement disorders and leukodystrophy.
- Targeted therapies for TUBB4A-related leukodystrophy necessitate validated tools for measuring mobility impairments.
- Existing gross motor outcome tools require evaluation for their efficacy in this specific pediatric cohort.
Purpose of the Study:
- To assess the utility of established gross motor function tools in a cohort of pediatric-onset TUBB4A-related leukodystrophy.
- To explore the performance of the Gross Motor Function Measure-88 (GMFM-88), Gross Motor Function Classification System-Expanded and Revised (GMFCS-ER), and Gross Motor Function Classification-Metachromatic Leukodystrophy (GMFC-MLD) in this population.
Main Methods:
- Thirty-five subjects with confirmed TUBB4A-related leukodystrophy were enrolled.
- Data collected included participant demographics, genotype, age at onset, and scores from GMFM-88, GMFCS-ER, and GMFC-MLD.
- Performance on each measure was compared, and a floor effect for GMFM-88 was defined as a total score below 20%.
Main Results:
- The median GMFM-88 performance was 16.24%, with 42.9% of individuals scoring above the defined floor effect.
- GMFM-88 Dimension A (Lying and Rolling) demonstrated the best performance, with 29 subjects scoring above the floor.
- Strong correlations were observed between GMFM-88 and both GMFCS-ER (r=0.90) and GMFC-MLD (r=0.88), as well as between GMFCS-ER and GMFC-MLD (r=0.92).
Conclusions:
- Despite an overall floor effect, the GMFM-88 effectively captures performance in individuals with milder TUBB4A-related leukodystrophy phenotypes.
- GMFM-88 Dimension A shows no floor effect, indicating its sensitivity across the spectrum of motor function.
- The GMFC-MLD shows strong correlation with other measures, supporting its use as an age-independent functional score in TUBB4A-related leukodystrophy.
