Brody Disease

Abstract

Brody disease is a rare muscle disorder characterized by exercise-induced progressive impairment of muscle relaxation, with stiffening, cramps, and myalgia which may be exacerbated by cold. Symptoms usually resolve after a few minutes’ rest and can affect upper and lower limbs and facial muscles (eyelids). This clinical picture has been described as “pseudo-myotonia” or “silent myotonia,” as no myotonic discharges are recorded from muscles and contractures are electrically silent. CK can be elevated and episodes of rhabdomyolysis and myoglobinuria may occur. Biochemical and immunocytochemical studies in muscle from patients show a marked reduction of Ca²⁺ uptake and Ca²⁺ ATPase activity in the sarcoplasmic reticulum of fast-twitch but not slow-twitch skeletal muscle fibers. Pathogenic mutations were identified in the ATP2A1 gene, encoding SERCA1 (Table 46.1), the fast-twitch skeletal muscle sarcoplasmic reticulum Ca²⁺ ATPase.