Stiffness on Exercise: a Non Progressive Disorder of Muscle Function (Brody-Karpati’s Syndrome)

Abstract

Muscle contracture or stiffness occurring with exercise is usually encountered in myotonic syndromes or muscle glycogenoses. However, in 1969 Irwin A. Brody described a new disorder of muscle function characterised by impaired muscle relaxation aggravated by exercise [1]. In this comprehensive paper with report of a single patient, he demonstrated that the most important biochemical finding was a marked decrease in the ability of the isolated sarcoplasmic reticulum to accumulate calcium ions. Reduced uptake of Ca²⁺ in isolated sarcoplasmic reticulum was suggested as the cause of the impaired muscle relaxation. In a series of collaborative studies, George Karpati confirmed that in this disorder a marked reduction of immunoreactive Ca²⁺ ATPase of the sarcoplasmic reticulum (SERCA) of fast - twitch muscle fibers (SERCA1) could be demonstrated [2, 3]. Mutations in the ATP2A1 gene (on chromosome 16q 12), encoding SERCA1, have been associated with autosomal recessive inheritance of Brody’s syndrome in 3 families, but not with autosomal dominant inheritance of the disease [4]. A search for mutations in the gene encoding sarcolipin, a SERCA1 - associated protein, did not reveal any alterations in 5 families [5].