International Paediatric Mitochondrial Disease Scale

Saskia Koene, Jan C M Hendriks, Ilse Dirks, Lonneke de Boer, Maaike C de Vries, Mirian C H Janssen, Izelle Smuts, Cheuk-Wing Fung, Virginia C N Wong, I René F M de Coo, Katharina Vill, Claudia Stendel, Thomas Klopstock, Marni J Falk, Elizabeth M McCormick, Robert McFarland, Imelda J M de Groot, Jan A M Smeitink, Saskia Koene, Jan C M Hendriks, Ilse Dirks, Lonneke de Boer, Maaike C de Vries, Mirian C H Janssen, Izelle Smuts, Cheuk-Wing Fung, Virginia C N Wong, I René F M de Coo, Katharina Vill, Claudia Stendel, Thomas Klopstock, Marni J Falk, Elizabeth M McCormick, Robert McFarland, Imelda J M de Groot, Jan A M Smeitink

Abstract

Objective: There is an urgent need for reliable and universally applicable outcome measures for children with mitochondrial diseases. In this study, we aimed to adapt the currently available Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) to the International Paediatric Mitochondrial Disease Scale (IPMDS) during a Delphi-based process with input from international collaborators, patients and caretakers, as well as a pilot reliability study in eight patients. Subsequently, we aimed to test the feasibility, construct validity and reliability of the IPMDS in a multicentre study.

Methods: A clinically, biochemically and genetically heterogeneous group of 17 patients (age 1.6-16 years) from five different expert centres from four different continents were evaluated in this study.

Results: The feasibility of the IPMDS was good, as indicated by a low number of missing items (4 %) and the positive evaluation of patients, parents and users. Principal component analysis of our small sample identified three factors, which explained 57.9 % of the variance. Good construct validity was found using hypothesis testing. The overall interrater reliability was good [median intraclass correlation coefficient for agreement between raters (ICCagreement) 0.85; range 0.23-0.99).

Conclusion: In conclusion, we suggest using the IPMDS for assessing natural history in children with mitochondrial diseases. These data should be used to further explore construct validity of the IPMDS and to set age limits. In parallel, responsiveness and the minimal clinically important difference should be studied to facilitate sample size calculations in future clinical trials.

Conflict of interest statement

Study fundingThe work of SK and JS was sponsored by ZonMW (The Netherlands Organization for Health Research and Development).Conflict of interestThis study was sponsored by ZonMW (The Netherlands Organization for Health Research and Development)Drs. Saskia Koene reports no disclosuresDr. Jan C.M. Hendriks reports no disclosuresIlse Dirks reports no disclosuresDr. Lonneke de Boer reports no disclosuresDrs. Maaike C. de Vries reports no disclosuresDr. Mirian C.H. Janssen reports no disclosuresProf. Izelle Smuts is an advisory board member for GenzymeCheuk-Wing Fung reports no disclosuresProf Virginia C.N. Wong reports no disclosuresDr. I. (René) F.M. de Coo reports no disclosuresDr. Katharina Vill reports no disclosuresDr. Claudia Stendel reports no disclosuresDr. Klopstock serves as a principal investigator or investigator on industry-sponsored trials funded by Santhera Pharmaceuticals and by GenSight Biologics. He has received research support from government entities (German Research Foundation; German Federal Ministry of Education and Research; European Commission 7th Framework Programme) and from commercial entities (Santhera Pharmaceuticals; Actelion Pharmaceuticals). He has been serving on scientific advisory boards for commercial entities (Santhera Pharmaceuticals; Actelion Pharmaceuticals) and for non-profit entities (Center for Rare Diseases Bonn, Germany; Hoffnungsbaum e.V., Germany). He has received speaker honoraria and travel costs from commercial entities (Santhera Pharmaceuticals; Actelion Pharmaceuticals; GenSight Biologics). He has been serving as a Section Editor for BMC Medical Genetics from 2011.Dr. Marni Falk holds stock options for serving on the scientific advisory board of Perlstein Laboratory, serves on the scientific advisory board of the non-profit Genesis Foundation, serves on the scientific and medical advisory board of the United Mitochondrial Disease Foundation, is a consultant for and receives research support from Mitobridge, and receives research support from Cardero Therapeutics, Vitaflo, Raptor Pharmaceuticals, as well as the National Institutes of Health (R01-HD065858, U54-HD086984, R01-GM115730)Elizabeth M. McCormick reports no disclosuresDr. Robert McFarland is supported by grants from the Wellcome Trust (0969/Z/11/Z), Medical Research Council UK (Kooo608), Lily Foundation (RES/0163/7553) and Ryan Stanford Appeal (RES/0163/7546)Imelda J.M. de Groot is consultant for Biomarin, PTC, Treat-NMD. She has collaborations in scientific projects on the development of technical aids (arm and hand exoskeletons) with Focal Meditech, Hankamp, BAAT Medical products, Summit, Laevo, Xsens, Maastricht Instruments. She has no financial interest in these firmsProf. Jan A.M. Smeitink is the founding CEO of Khondrion BV

References

    1. Abel MF, Damiano DL, Blanco JS, et al. Relationships among musculoskeletal impairments and functional health status in ambulatory cerebral palsy. J Pediatr Orthop. 2003;23(4):535–541.
    1. Administration FaD (2009) FDA Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims.
    1. Beenakker EA, Maurits NM, Fock JM, Brouwer OF, van der Hoeven JH. Functional ability and muscle force in healthy children and ambulant Duchenne muscular dystrophy patients. Eur J Paediatr Neurol. 2005;9(6):387–393. doi: 10.1016/j.ejpn.2005.06.004.
    1. Beghi E, Regio V, Papantonio A, et al. Reliability of clinical diagnosis of dystonia. Neuroepidemiology. 2014;43(3–4):213–219. doi: 10.1159/000367628.
    1. Bella GP, Rodrigues NB, Valenciano PJ, Silva LM, Souza RC. Correlation among the visual gait assessment scale, edinburgh visual gait scale and observational gait scale in children with spastic diplegic cerebral palsy. Rev Bras Fisioter. 2012;16(2):134–140. doi: 10.1590/S1413-35552012000200009.
    1. Blanchet L, Smeitink JA, van Emst-de Vries SE, et al. Quantifying small molecule phenotypic effects using mitochondrial morpho-functional fingerprinting and machine learning. Sci Rep. 2015;5:8035. doi: 10.1038/srep08035.
    1. Hsue BJ, Chen YJ, Wang YE. The intra- and inter-rater reliability of component analysis of rise from supine in the children with typical development and developmental delay. Res Dev Disabil. 2014;35(1):162–170. doi: 10.1016/j.ridd.2013.10.011.
    1. Koene S, Smeitink J. Mitochondrial medicine: entering the era of treatment. J Intern Med. 2009;265(2):193–209. doi: 10.1111/j.1365-2796.2008.02058.x.
    1. Koene S, Jansen M, Verhaak CM, De Vrueh RL, De Groot IJ, Smeitink JA (2013a) Towards the harmonization of outcome measures in children with mitochondrial disorders. Dev Med Child Neurol
    1. Koene S, Wortmann SB, de Vries MC et al (2013b) Developing outcome measures for pediatric mitochondrial disorders: which complaints and limitations are most burdensome to patients and their parents? Mitochondrion 13(1):15–24
    1. Koopman WJ, Willems PH, Smeitink JA. Monogenic mitochondrial disorders. N Engl J Med. 2012;366(12):1132–1141. doi: 10.1056/NEJMra1012478.
    1. Miller TM, Johnston SC. Should the Babinski sign be part of the routine neurologic examination? Neurology. 2005;65(8):1165–1168. doi: 10.1212/01.wnl.0000180608.76190.10.
    1. Parreira SL, Resende MB, Zanoteli E, Carvalho MS, Marie SK, Reed UC. Comparison of motor strength and function in patients with Duchenne muscular dystrophy with or without steroid therapy. Arq Neuropsiquiatr. 2010;68(5):683–688. doi: 10.1590/S0004-282X2010000500002.
    1. Peng M, Ostrovsky J, Kwon YJ, et al. Inhibiting cytosolic translation and autophagy improves health in mitochondrial disease. Hum Mol Genet. 2015;24(17):4829–4847. doi: 10.1093/hmg/ddv207.
    1. Phoenix C, Schaefer AM, Elson JL, et al. A scale to monitor progression and treatment of mitochondrial disease in children. Neuromuscul Disord. 2006;16(12):814–820. doi: 10.1016/j.nmd.2006.08.006.
    1. Sanger TD, Delgado MR, Gaebler-Spira D, Hallett M, Mink JW. Classification and definition of disorders causing hypertonia in childhood. Pediatrics. 2003;111(1):e89–e97. doi: 10.1542/peds.111.1.e89.
    1. Schaefer AM, Taylor RW, Turnbull DM, Chinnery PF. The epidemiology of mitochondrial disorders--past, present and future. Biochim Biophys Acta. 2004;1659(2–3):115–120. doi: 10.1016/j.bbabio.2004.09.005.
    1. Singerman J, Lee L. Consistency of the Babinski reflex and its variants. Eur J Neurol. 2008;15(9):960–964. doi: 10.1111/j.1468-1331.2008.02219.x.
    1. Vet HTCM, Mokkink LB, Knol DL. Measurement in medicine. Cambridge: Cambridge University Press; 2011.
    1. Viscomi C, Bottani E, Civiletto G, et al. In vivo correction of COX deficiency by activation of the AMPK/PGC-1alpha axis. Cell Metab. 2011;14(1):80–90. doi: 10.1016/j.cmet.2011.04.011.
    1. Viscomi C, Bottani E, Zeviani M. Emerging concepts in the therapy of mitochondrial disease. Biochim Biophys Acta. 2015;1847(6–7):544–557. doi: 10.1016/j.bbabio.2015.03.001.
    1. Wenz T. PGC-1alpha activation as a therapeutic approach in mitochondrial disease. IUBMB Life. 2009;61(11):1051–1062. doi: 10.1002/iub.261.
    1. Wright A, Hannon J, Hegedus EJ, Kavchak AE. Clinimetrics corner: a closer look at the minimal clinically important difference (MCID) J Manual Man Ther. 2012;20(3):160–166. doi: 10.1179/2042618612Y.0000000001.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться