Abstract:

Introduction: In presence of proximal muscle weakness, normal CPK, myopathic EMG pattern, muscle biopsy showing red ragged fibres and MRI showing changes in corpus callosum and white matter, mitochondrial disorder seems most likely and confirmation needs mitochondrial genome analysis.

Methods: Four children from 2 unrelated families  presented to us with proximal muscle weakness.  Investigations revealed normal CPK and myopathic pattern on electromyography. The muscle biopsy showed normal immunohistochemistry with preserved fascicular architecture with focal areas of degeneration and regeneration with few ragged red fibers. In view of the presence of ragged red fibers, a mitochondrial disorder was considered and an MRI brain was obtained. The MRI showed a peculiar pattern of corpus callosum and cerebral hemispheric white matter involvement but possibly suggestive of a mitochondrial disorder.

Result: In consultation with international experts, the children’s samples were sent to participate in a whole genome sequencing study. This revealed mutation in a congenital myasthenia gene in both the families, establishing a diagnosis of limb girdle form of congenital myasthenic syndrome. Repetitive nerve stimulation was performed which showed electrodecremental response.

Conclusion: The children were started on pyridostigmine with resultant improvement in the weakness and exercise tolerance. Congenital myasthenic syndrome due to this gene typically has a limb-girdle pattern of weakness without ptosis and may present without the typical myasthenic diurnal variation in weakness. White matter abnormalities have not been described in the reported patients so far.