Myopathy with Deficiency of ISCU – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

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NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.

CLINICAL CHARACTERISTICS

Myopathy with deficiency of ISCU, a mitochondrial myopathy, is classically characterized by lifelong exercise intolerance in which minor exertion causes tachycardia, shortness of breath, fatigue, and pain of active muscles; episodes of more profound exercise intolerance associated with rhabdomyolysis, myoglobinuria, and weakness that may be severe; and typically full recovery of muscle strength between episodes of rhabdomyolysis. Affected individuals usually have near-normal strength; they can have large calves.

DIAGNOSIS/TESTING: The diagnosis of myopathy with deficiency of ISCU is established in a proband by the identification of biallelic pathogenic variants in by molecular genetic testing or, if molecular genetic testing is uninformative, by characteristic histochemical and biochemical findings on muscle biopsy.

MANAGEMENT

Anecdotal evidence suggests that episodes of rhabdomyolysis and myoglobinuria may be prevented by avoiding sustained fatiguing physical exertion. The major secondary complications are those attributable to rhabdomyolysis and myoglobinuria, including renal failure and hyperkalemia. Management is similar to that for other causes of rhabdomyolysis Sustained fatiguing physical exertion.

GENETIC COUNSELING

Myopathy with deficiency of ISCU is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased are possible if the pathogenic variants in the family have been identified.