International Paediatric Mitochondrial Disease Scale.
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.



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.



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).



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.
Radboudn Center for Mitochondrial Medicine at the Department of Paediatrics, Radboudumc, Geert Grooteplein 10. 6500 HB, PO BOX 9101, Nijmegen, The Netherlands. Saskia.koene@radboudumc.nl.
Saskia
S
Koene
Department of Health Evidence, Radboudumc, Nijmegen, The Netherlands.
Jan C M
JCM
Hendriks
Radboudn Center for Mitochondrial Medicine at the Department of Paediatrics, Radboudumc, Geert Grooteplein 10. 6500 HB, PO BOX 9101, Nijmegen, The Netherlands.
Ilse
I
Dirks
Radboudn Center for Mitochondrial Medicine at the Department of Paediatrics, Radboudumc, Geert Grooteplein 10. 6500 HB, PO BOX 9101, Nijmegen, The Netherlands.
Lonneke
L
de Boer
Radboudn Center for Mitochondrial Medicine at the Department of Paediatrics, Radboudumc, Geert Grooteplein 10. 6500 HB, PO BOX 9101, Nijmegen, The Netherlands.
Maaike C
MC
de Vries
Radboudn Center for Mitochondrial Medicine at the Department of Paediatrics, Radboudumc, Geert Grooteplein 10. 6500 HB, PO BOX 9101, Nijmegen, The Netherlands.
Mirian C H
MCH
Janssen
Steve Biko Academic Hospital, Ludwig-Maximilians-of Pretoria, Pretoria, South Africa.
Izelle
I
Smuts
Department of Paediatrics & Adolescent Medicine, University of Hong Kong, Hong Kong, Hong Kong.
Cheuk-Wing
CW
Fung
Department of Paediatrics & Adolescent Medicine, University of Hong Kong, Hong Kong, Hong Kong.
Virginia C N
VCN
Wong
Department of Neurology, ErasmusMC, Rotterdam, The Netherlands.
I René F M
IRFM
de Coo
Department of Pediatric Neurology and Developmental Medicine, Dr. v. Hauner Children's Hospital, Ludwig-Maximilians-University, Munich, Germany.
Katharina
K
Vill
Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich, Germany.|German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Claudia
C
Stendel
Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich, Germany.|German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.|Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
Thomas
T
Klopstock
Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Marni J
MJ
Falk
Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Elizabeth M
EM
McCormick
Wellcome Trust Centre for Mitochondrial Research Newcastle, Newcastle upon Tyne, UK.
Robert
R
McFarland
Radboudn Center for Mitochondrial Medicine at the Department of Paediatrics, Radboudumc, Geert Grooteplein 10. 6500 HB, PO BOX 9101, Nijmegen, The Netherlands.|Department of Rehabilitation, Radboudumc, Nijmegen, The Netherlands.
Imelda J M
IJM
de Groot
Radboudn Center for Mitochondrial Medicine at the Department of Paediatrics, Radboudumc, Geert Grooteplein 10. 6500 HB, PO BOX 9101, Nijmegen, The Netherlands.
Jan A M
JAM
Smeitink
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008928:Mitochondria / Q000473:pathology; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000473:pathology; D025341:Principal Component Analysis / Q000379:methods; D015203:Reproducibility of Results