Mitochondrial myopathy with tRNA Leu(UUR) mutation and complex I deficiency responsive to riboflavin☆,☆☆
Section snippets
CASE REPORTS
The proband (III-2 in Fig. 1) is the second child of nonconsanguineous Australian parents. Birth weight was 3317 gm (25th to 50th percentile). Early developmental milestones were normal. The girl smiled at 2 months of age, sat independently at 5 months, and was
Muscle histochemistry, electron microscopy, and enzymology
An open muscle biopsy was performed initially on the left quadriceps. Sections of muscle were stained with hematoxylin-eosin, modified Gomori trichrome, oil red O, lactate dehydrogenase succinate dehydrogenase, and cytochrome c oxidase. Electron microscopy was also performed.
A repeated open quadriceps biopsy was performed when the patient was 2 ½ years of age for respiratory chain enzyme analysis and repeated enzyme histochemistry study. Respiratory chain complexes I (rotenone-sensitive
Muscle histochemistry and electron microscopy
A muscle biopsy performed at when the patient was 2 ½ years of age showed type I fibers to have an increase in lipid droplets. The mitochondrial stains were abnormal, with increased numbers of subsarcolemmal mitochondria in the modified Gomori trichrome, succinic dehydrogenase, and cytochrome c oxidase stains. The staining pattern was not sufficiently abnormal, however, to be called true ragged red fibers (Fig. 3).
DISCUSSION
There have been only a few reports of the pure myopathic form of complex I deficiency that have been responsive to treatment. However, there has been no systematic reporting of unresponsive patients. At initial diagnosis, our patient was presumed to have an isolated complex I defect, because all other enzymes were in the normal range and no definite cytochrome c oxidase–negative fibers were found. Clinically she had an unequivocally positive response to riboflavin during a 3-year period. Some
Acknowledgements
We thank Dr. John Walsh, Department of Neurology, Royal Prince Alfred Hospital, Camperdown, for reporting on the microscopy of the muscle biopsy specimen, Prof. David Sillence, Head of Department of Clinical Genetics, Royal Alexandra Hospital for Children, Westmead, for his assistance in the photography of the muscle biopsy specimen, Dr. Xenia Dennett for her examination of postmortem muscle samples from the sibling, and Dr. Alex Kan, Department of Histopathology, Royal Alexandra Hospital for
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