PMID- 37461315
OWN - NLM
STAT- MEDLINE
DCOM- 20230911
LR  - 20231003
IS  - 1708-8283 (Electronic)
IS  - 0883-0738 (Print)
IS  - 0883-0738 (Linking)
VI  - 38
IP  - 8-9
DP  - 2023 Aug
TI  - Gross Motor Function in Pediatric Onset TUBB4A-Related Leukodystrophy: GMFM-88 
      Performance and Validation of GMFC-MLD in TUBB4A.
PG  - 498-504
LID - 10.1177/08830738231188159 [doi]
AB  - 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.
FAU - Gavazzi, Francesco
AU  - Gavazzi F
AUID- ORCID: 0000-0002-4908-8395
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Patel, Virali
AU  - Patel V
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Charsar, Brittany
AU  - Charsar B
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Glanzman, Allan
AU  - Glanzman A
AD  - Department of Physical Therapy, Children's Hospital of Philadelphia, 
      Philadelphia, PA, USA.
FAU - Erler, Jacqueline
AU  - Erler J
AUID- ORCID: 0000-0001-6364-0089
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Sevagamoorthy, Anjana
AU  - Sevagamoorthy A
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - McKenzie, Emma
AU  - McKenzie E
AD  - Department of Physical Therapy, Children's Hospital of Philadelphia, 
      Philadelphia, PA, USA.
FAU - Kornafel, Tracy
AU  - Kornafel T
AD  - Department of Physical Therapy, Children's Hospital of Philadelphia, 
      Philadelphia, PA, USA.
FAU - Ballance, Elizabeth
AU  - Ballance E
AUID- ORCID: 0000-0002-6742-6992
AD  - Department of Physical Therapy, Children's Hospital of Philadelphia, 
      Philadelphia, PA, USA.
FAU - Pierce, Samuel R
AU  - Pierce SR
AD  - Department of Physical Therapy, Children's Hospital of Philadelphia, 
      Philadelphia, PA, USA.
FAU - Teng, Michelle
AU  - Teng M
AD  - Synaptixbio Ltd, Oxfordshire, United Kingdom.
FAU - Formanowski, Brielle
AU  - Formanowski B
AD  - Division of Neonatology, Department of Pediatrics, Children's Hospital of 
      Philadelphia, Philadelphia, PA, USA.
FAU - Woidill, Sarah
AU  - Woidill S
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Shults, Justine
AU  - Shults J
AD  - Synaptixbio Ltd, Oxfordshire, United Kingdom.
FAU - Wassmer, Evangeline
AU  - Wassmer E
AD  - Neurology Department, Birmingham Children's Hospital, Institute of Health and 
      Neurodevelopment, Aston University, Birmingham, United Kingdom.
FAU - Tonduti, Davide
AU  - Tonduti D
AD  - Unit of Pediatric Neurology, COALA (Center for Diagnosis and Treatment of 
      Leukodystrophies), V. Buzzi Children's Hospital, Milan, Italy.
AD  - Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, 
      Universita degli Studi di Milano, Milan, Italy.
FAU - Magrinelli, Francesca
AU  - Magrinelli F
AD  - Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of 
      Neurology, University College London, London, United Kingdom.
FAU - Bernard, Genevieve
AU  - Bernard G
AD  - Departments of Neurology and Neurosurgery, Pediatrics and Human Genetics, McGill 
      University, Montreal, QC, Canada.
AD  - Department Specialized Medicine, Division of Medical Genetics, McGill University 
      Health Centre, Montreal, QC, Canada.
AD  - Child Health and Human Development Program, Research Institute of the McGill 
      University Health Centre, Montreal, QC, Canada.
FAU - Van Der Knaap, Marjo
AU  - Van Der Knaap M
AD  - Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's 
      Hospital, Amsterdam University Medical Centers, and Amsterdam Neuroscience, 
      Cellular & Molecular Mechanisms, Vrije Universiteit, Amsterdam, the Netherlands.
AD  - Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive 
      Research, Vrije Universiteit, Amsterdam, the Netherlands.
FAU - Wolf, Nicole
AU  - Wolf N
AD  - Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's 
      Hospital, Amsterdam University Medical Centers, and Amsterdam Neuroscience, 
      Cellular & Molecular Mechanisms, Vrije Universiteit, Amsterdam, the Netherlands.
FAU - Adang, Laura
AU  - Adang L
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
AD  - Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 
      Philadelphia, PA, USA.
FAU - Vanderver, Adeline
AU  - Vanderver A
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
AD  - Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 
      Philadelphia, PA, USA.
LA  - eng
GR  - K23 NS114113/NS/NINDS NIH HHS/United States
GR  - U54 NS115052/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230717
PL  - United States
TA  - J Child Neurol
JT  - Journal of child neurology
JID - 8606714
RN  - 0 (TUBB4A protein, human)
RN  - 0 (Tubulin)
SB  - IM
MH  - Humans
MH  - *Leukodystrophy, Metachromatic/complications
MH  - *Cerebral Palsy
MH  - *Movement Disorders/complications
MH  - Reproducibility of Results
MH  - Severity of Illness Index
MH  - Motor Skills
MH  - Tubulin/genetics
PMC - PMC10527384
MID - NIHMS1914118
OTO - NOTNLM
OT  - GMFC-MLD
OT  - GMFM-88
OT  - TUBB4A
OT  - gross motor
OT  - leukodystrophy
COIS- AV receives grant and in-kind support for research from Eli Lilly, Gilead, 
      Takeda, Illumina, Biogen, Homology, Ionis, Passage Bio, Orchard Therapeutics. AV 
      serves on the scientific advisory boards of the European Leukodystrophy 
      Association and the United Leukodystrophy Foundation, as well as in an unpaid 
      capacity for Takeda, Ionis, Biogen and Illumina. LAA is a consultant for Takeda, 
      Biogen, and Orchard Therapeutics. GB is/was a consultant for Passage Bio Inc 
      (2020-2022) and Ionis (2019). She is/was a site investigator for the Alexander's 
      disease trial of Ionis (2021-now), Metachromatic leukodystrophy of Shire/Takeda 
      (2020-2021), Krabbe and GM1 gene therapy trials of Passage Bio (2021-now), 
      Passage Bio GM1 natural history study (2021-now) and 
      Adrenoleukodystrophy/Hematopoietic stem cell transplantation natural history 
      study of Bluebird Bio (2019), a site sub-investigator for the MPS II gene therapy 
      trial of Regenxbio (2021-now) and the MPS II clinical trial of Denali (2022-now). 
      She has received an unrestricted educational grant from Takeda (2021-2022). She 
      serves on the scientific advisory board of the Pelizaeus-Merzbacher Foundation, 
      the Yaya Foundation Scientific and Clinical Advisory Council and is the Chair of 
      the Medical and Scientific Advisory Board of the United Leukodystrophy 
      Foundation. She is a member of the Vanishing White Matter Consortium, the H-ABC 
      Clinical Advisory Board and the Chair of the POLR3-related (4H) Leukodystrophy 
      Consortium. She is on the editorial boards of Neurology Genetics, Frontiers in 
      Neurology - Neurogenetics, and Journal of Medical Genetics.
EDAT- 2023/07/18 06:42
MHDA- 2023/09/11 06:43
PMCR- 2023/09/27
CRDT- 2023/07/18 02:53
PHST- 2023/09/11 06:43 [medline]
PHST- 2023/07/18 06:42 [pubmed]
PHST- 2023/07/18 02:53 [entrez]
PHST- 2023/09/27 00:00 [pmc-release]
AID - 10.1177/08830738231188159 [doi]
PST - ppublish
SO  - J Child Neurol. 2023 Aug;38(8-9):498-504. doi: 10.1177/08830738231188159. Epub 
      2023 Jul 17.