Amyotrophic lateral sclerosis with ragged-red fibers.

BACKGROUND

Motor neuron diseases (amyotrophic lateral sclerosis [ALS] and spinal muscular atrophy [SMA]) have been rarely associated with mitochondrial respiratory chain defects.

OBJECTIVES

To describe a patient with typical ALS and the finding of ragged-red fibers in muscle biopsy specimens and to review the literature on respiratory chain defects in ALS and SMA.

DESIGN

Case report and review of the literature.

SETTING

Collaboration between tertiary care academic hospitals.

PATIENT: A 65-year-old man with typical ALS.

MAIN OUTCOME MEASURES: The patient had 10% ragged-red fibers and 3% cytochrome-c oxidase-negative fibers in muscle biopsy specimens but no biochemical defects of respiratory chain enzymes or alterations of mitochondrial DNA (mtDNA).

RESULTS

Amyotrophic lateral sclerosis with ragged-red fibers has been reported in 5 families and is associated with mtDNA mutations in some subjects. Spinal muscular atrophy without mutations in the survival motor neuron gene (SMN; OMIM 600354) has been associated with mtDNA depletion or with mutations in the cytochrome-c oxidase assembly gene (SCO2; OMIM 604377).

CONCLUSION

Respiratory chain defects can mimic ALS or SMA and should be considered in the differential diagnosis.