Abstract Details

Title Ryanodine Receptor RYR1 Gene Mutations in African American Men with Hypertrophied Muscles and Persistently Elevated Serum Creatine Kinase

Topic Muscle Disease/Neuromuscular Junction

Presentation(s) S05 - (-)

Poster/Presentation
Number 004

Objective

Background Muscle hypertrophy with cramps and elevated serum CK are caused by disorders of dystrophin, sarcoglycans, caveolin, deficiencies in enzymes of glycolysis and lipolysis. Mutations in RYR1 gene cause central core, core- rod myopathy, malignant hyperthermia and exertional rhabdomyolysis. RYR1 plays role in excitation- contraction coupling.

Design/Methods Seven African American men presented with muscle cramps and pain and made worse with exertion. All had strong muscles. None of them had muscle tenderness, myotonia, muscle rippling or myoedema. Two had exerional myoglobinuria. None of them had an adverse anesthetic reaction. Serum CK ranged from 400 to 1500 IU. Electromyography was normal. Metabolic studies on plasma and urine were normal Muscle biopsies (6/7) showed non specific changes: variation in fiber size, increase in fibers with central muscles and in 2 patients disorganization on NADH-TR stain.

Results All had heterozygous mutations. Two patients had 2 mutations , one had 3 mutations and 4 had single point mutation. Four mutations were previously described in patients with malignant hyperthermia (exon 2 94 C>T, exon 28 C.4055C>G, exon 91 C.1288C>T, exon 91 C.12869Dup9, exon 28 C.4055C>G.) Two mutations associated with exertional rhabdomyolysis (exon 23 C.2797G>A, exon 63 C.9242T>C). Three were previously unreported. (exon C.9353C>T, exon 76 C.11061_11063DELGGA, exon 57 C.8693-25C>T splice site).

Conclusions Mutations in RYR1 is associated with hypertrophied muscles, cramp and persistently elevated serum CK Some mutations are associated with risk for malignant hyperthermia and exertion rhabdomyolysis. Screening for RYR1 gene mutations should be part of evaluation of hyperCK emia syndrome .

Authors/Disclosures
V V. Vedanarayanan, MD, FRCPC (University of Texas at Austin, Dell Medical School) PRESENTER	Dr. Vedanarayanan has nothing to disclose.
David J. Sinclair, MD (Merit Health Medical Group - Neurology)	No disclosure on file
Jeffrey L. Saver, MD, FAAN (UCLA Health)	Dr. Saver has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medtronic. Dr. Saver has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Stryker. Dr. Saver has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cerenovus. Dr. Saver has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boehringer Ingelheim (prevention only). Dr. Saver has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Medical Association. Dr. Saver has received stock or an ownership interest from Rapid Medical.

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