Mitochondrial disease criteria: diagnostic applications in children.
BACKGROUND
Based on a previous prospective clinical and biochemical study, a consensus mitochondrial disease scoring system was established to facilitate the diagnosis in patients with a suspected mitochondrial disorder.


OBJECTIVE
To evaluate the specificity of the diagnostic system, we applied the mitochondrial disease score in 61 children with a multisystem disease and a suspected oxidative phosphorylation disorder who underwent a muscle biopsy and were consecutively diagnosed with a genetic mutation.


METHODS
We evaluated data of 44 children diagnosed with a disorder in oxidative phosphorylation, carrying a mutation in the mitochondrial or nuclear DNA. We compared them with 17 children who, based on the clinical and metabolic features, also had a muscle biopsy but were finally diagnosed with a nonmitochondrial multisystem disorder by further genetic analysis.


RESULTS
All children with a genetically established diagnosis of a primary oxidative phosphorylation disorder had a mitochondrial disease score above 6 (probable mitochondrial disorder), and 73% of the children had a score above 8 (definite mitochondrial disorder) at evaluation of the muscle biopsy. In the nonmitochondrial multisystem disorder group, the score was significantly lower, and no patients reached a score comparable with a definite respiratory chain disorder.


CONCLUSIONS
The mitochondrial disease criteria system has a high specificity to distinguish between mitochondrial and other multisystem disorders. The method could also be applied in children with a suspected mitochondrial disorder, prior to performing a muscle biopsy.
Morava
E
E
Department of Pediatrics, Nijmegen Centre for Mitochondrial Disorders, Radboud University Medical Centre Nijmegen, PO Box 9101, 6500 HB Nijmegen, the Netherlands. E.Morava@cukz.umcn.nl
van den Heuvel
L
L
Hol
F
F
de Vries
M C
MC
Hogeveen
M
M
Rodenburg
R J
RJ
Smeitink
J A M
JA
D001706:Biopsy / Q000592:standards; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods / Q000592:standards; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods / Q000592:standards; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009135:Muscular Diseases / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D011237:Predictive Value of Tests
D004272:DNA, Mitochondrial