Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2017

Open Access 01-12-2017 | Research

Quantification of gait in mitochondrial m.3243A > G patients: a validation study

Authors: Rob Ramakers, Saskia Koene, Jan T Groothuis, Paul de Laat, Mirian CH Janssen, Jan Smeitink

Published in: Orphanet Journal of Rare Diseases | Issue 1/2017

Login to get access

Abstract

Background

More than half of the patients harbouring the m.3243A > G mutation were found to have trouble maintaining balance when walking in a recent study by our group. Others demonstrated that these patients had an abnormal gait pattern, as quantified by gait analysis. Gait analysis is an emerging method to quantify subtle changes in walking pattern, also during therapeutic interventions. Therefore, we aimed to test the reliability and reproducibility of gait analysis and select the most suitable protocol for this group of patients using a GAITRite electronic walkway. Four different protocols were tested: normal walking, dual task, post exercise and after a ten minutes of rest.

Results

In total 36 patients with the m.3243A > G mutation and 50 healthy controls were enrolled in this study. Overall high intra class correlation coefficients were found in all experimental conditions for both patients and healthy controls indicating good reproducibility. Marked differences in gait between patients and controls were observed and were in line with the only available exploratory study performed. There was a good correlation between both the overall NMDAS score, NMDAS subscale scores, both markers for disease severity, and specific gait parameters.

Conclusions

The observed reliability of the test makes GAITRite a suitable instrument for intervention studies in patients with mitochondrial disease.
Literature
1.
Calvo SE, Clauser KR, Mootha VK. MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins. Nucleic Acids Res. 2016;44:D1251–1257.CrossRefPubMed
2.
Pagliarini DJ, Calvo SE, Chang B, Sheth SA, Vafai SB, Ong SE, Walford GA, Sugiana C, Boneh A, Chen WK, et al. A mitochondrial protein compendium elucidates complex I disease biology. Cell. 2008;134:112–23.CrossRefPubMedPubMedCentral
3.
Pfeffer G, Majamaa K, Turnbull DM, Thorburn D, Chinnery PF. Treatment for mitochondrial disorders. Cochrane Database Syst Rev. 2012;4:CD004426.
4.
Gorman GS, Schaefer AM, Ng Y, Gomez N, Blakely EL, Alston CL, Feeney C, Horvath R, Yu-Wai-Man P, Chinnery PF, et al. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann Neurol. 2015;77:753–9.CrossRefPubMedPubMedCentral
5.
Nesbitt V, Pitceathly RD, Turnbull DM, Taylor RW, Sweeney MG, Mudanohwo EE, Rahman S, Hanna MG, McFarland R. The UK MRC mitochondrial disease patient cohort study: clinical phenotypes associated with the m.3243A > G mutation--implications for diagnosis and management. J Neurol Neurosurg Psychiatry. 2013;84:936–8.CrossRefPubMed
6.
de Laat P, Koene S, van den Heuvel LP, Rodenburg RJ, Janssen MC, Smeitink JA. Clinical features and heteroplasmy in blood, urine and saliva in 34 dutch families carrying the m.3243A > G mutation. J Inherit Metab Dis. 2012;35:1059–69.CrossRefPubMedPubMedCentral
7.
Galna B, Newman J, Jakovljevic DG, Bates MG, Schaefer AM, McFarland R, Turnbull DM, Trenell MI, Gorman GS, Rochester L. Discrete gait characteristics are associated with m.3243A > G and m.8344A > G variants of mitochondrial disease and its pathological consequences. J Neurol. 2014;261:73–82.CrossRefPubMed
8.
Galna B, Lord S, Rochester L. Is gait variability reliable in older adults and Parkinson’s disease? towards an optimal testing protocol. Gait Posture. 2013;37:580–5.CrossRefPubMed
9.
Pradhan C, Wuehr M, Akrami F, Neuhaeusser M, Huth S, Brandt T, Jahn K, Schniepp R. Automated classification of neurological disorders of gait using spatio-temporal gait parameters. J Electromyogr Kinesiol. 2015;25:413–22.CrossRefPubMed
10.
Godinho C, Domingos J, Cunha G, Santos AT, Fernandes RM, Abreu D, Goncalves N, Matthews H, Isaacs T, Duffen J, et al. A systematic review of the characteristics and validity of monitoring technologies to assess Parkinson’s disease. J Neuroeng Rehabil. 2016;13:24.CrossRefPubMedPubMedCentral
11.
Hollands KL, Pelton TA, van der Veen S, Alharbi S, Hollands MA. A novel and simple test of gait adaptability predicts gold standard measures of functional mobility in stroke survivors. Gait Posture. 2016;43:170–5.CrossRefPubMed
12.
Koopman WJ, Willems PH, Smeitink JA. Monogenic mitochondrial disorders. N Engl J Med. 2012;366:1132–41.CrossRefPubMed
13.
Lord S, Galna B, Verghese J, Coleman S, Burn D, Rochester L. Independent domains of gait in older adults and associated motor and nonmotor attributes: validation of a factor analysis approach. J Gerontol A Biol Sci Med Sci. 2013;68:820–7.CrossRefPubMed
14.
Schaefer AM, Phoenix C, Elson JL, McFarland R, Chinnery PF, Turnbull DM. Mitochondrial disease in adults: a scale to monitor progression and treatment. Neurology. 2006;66:1932–4.CrossRefPubMed
15.
Berg KO, Wood-Dauphinee SL, Williams JI, Maki B. Measuring balance in the elderly: validation of an instrument. Can J Public Health. 1992;83 Suppl 2:S7–11.PubMed
16.
Ebersbach G, Dimitrijevic MR, Poewe W. Influence of concurrent tasks on gait: a dual-task approach. Percept Mot Skills. 1995;81:107–13.CrossRefPubMed
17.
Schniepp R, Wuehr M, Neuhaeusser M, Kamenova M, Dimitriadis K, Klopstock T, Strupp M, Brandt T, Jahn K. Locomotion speed determines gait variability in cerebellar ataxia and vestibular failure. Mov Disord. 2012;27:125–31.CrossRefPubMed
18.
Wuehr M, Schniepp R, Ilmberger J, Brandt T, Jahn K. Speed-dependent temporospatial gait variability and long-range correlations in cerebellar ataxia. Gait Posture. 2013;37:214–8.CrossRefPubMed
19.
Maki BE. Gait changes in older adults: predictors of falls or indicators of fear. J Am Geriatr Soc. 1997;45:313–20.CrossRefPubMed
20.
Verghese J, Holtzer R, Lipton RB, Wang C. Quantitative gait markers and incident fall risk in older adults. J Gerontol A Biol Sci Med Sci. 2009;64:896–901.CrossRefPubMed
21.
Snijders AH, van de Warrenburg BP, Giladi N, Bloem BR. Neurological gait disorders in elderly people: clinical approach and classification. Lancet Neurol. 2007;6:63–74.CrossRefPubMed
Metadata
Title
Quantification of gait in mitochondrial m.3243A > G patients: a validation study
Authors
Rob Ramakers
Saskia Koene
Jan T Groothuis
Paul de Laat
Mirian CH Janssen
Jan Smeitink
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2017
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-017-0644-y

Other articles of this Issue 1/2017

Orphanet Journal of Rare Diseases 1/2017 Go to the issue

Research

Diagnosis features of pediatric Gaucher disease patients in the era of enzymatic therapy, a national-base study from the Spanish Registry of Gaucher Disease

Research

A quantitative assessment of the evolution of cerebellar syndrome in children with phosphomannomutase-deficiency (PMM2-CDG)

Position statement

Critical appraisal of arguments for the delayed-start design proposed as alternative to the parallel-group randomized clinical trial design in the field of rare disease

Research

Prevalence and risk factors for type 2 diabetes mellitus with Prader–Willi syndrome: a single center experience

Research

Phenotype prediction for mucopolysaccharidosis type I by in silico analysis

Research

The burden of amyloid light chain amyloidosis on health-related quality of life