J. Uusimaa et al., Childhood encephalopathies and myopathies: A prospective study in a defined population to assess the frequency of mitochondrial disorders, PEDIATRICS, 105(3), 2000, pp. 598-603
Objectives. To assess the frequency of mitochondrial abnormalities in muscl
e histology, defects in respiratory chain enzyme activities, and mutations
in mitochondrial DNA (mtDNA) in children with unexplained psychomotor retar
dation in the population of Northern Finland.
Background. The frequency of mitochondrial diseases among patients with chi
ldhood encephalopathies and myopathies is not known. Frequencies are diffic
ult to estimate because the clinical presentation of these disorders is var
iable.
Methods. A total of 116 consecutive patients with undefined encephalopathie
s and myopathies were enrolled during a 7-year period in a hospital serving
as the only neurologic unit for a pediatric population of 97 609 and as th
e only tertiary level neurologic unit for a pediatric population of 48 873.
Biochemical and morphologic investigations were performed on muscle biopsy
material, including oximetric and spectrophotometric analyses of oxidative
phosphorylation, histochemistry, electron microscopy, and molecular analys
is of mtDNA.
Results. Ultrastructural changes in the mitochondria were the most common f
inding in the muscle biopsies (71%). Ragged-red fibers were found in 4 case
s. An oxidative phosphorylation defect was found in 26 children (28%), comp
lex I (n = 15) and complex IV (n = 13) defects being the most common. Fifte
en percent of patients (n = 17/116) with unexplained encephalomyopathy or m
yopathy had a probable mitochondrial disease. Common pathogenic mutations w
ere found in the mtDNA of only 1 patient (.9%).
Conclusions. The common known mutations in mtDNA are rarely causes of child
hood encephalomyopathies, which is in contrast to the considerable frequenc
y of the common MELAS mutation observed among adults in the same geographic
al area. Biochemically and morphologically verified mitochondrial disorders
were nevertheless common among the children, making the analysis of a musc
le biopsy very important for clinical diagnostic purposes.