Idiopathic HyperCKemia

Abstract & Commentary

By Michael Rubin, MD, Professor of Clinical Neurology, NewYork-Presbyterian Hospital, Cornell Campus. Dr. Rubin is on the speaker's bureau for Athena Diagnostics, and does research for Pfizer and Merck.

Synopsis: Persistent elevation of serum CK without symptoms should be aggressively investigated, including a muscle biopsy, since half will have HyperCKemia, and half will have a specific pathology.

Source: Capasso M, et al. Familial Idiopathic HyperCKemia: An Underrecognized Condition. Muscle Nerve. 2006;33:760-765.

Persistently elevated serum creatine kinase (CK) raises the specter of myopathy, although idiopathic hyperCKemia (IH) may ultimately be the final diagnosis. Not as well recognized is a familial variant that may be more frequent than previously appreciated. Among 1100 neuromuscular patients seen over an 11-year period, 42 were felt to have probable IH based on persistent serum CK elevation, normal neurological examination, no history of myotoxic drug intake, no exercise-induced muscle cramps or myoglobinuria, no family history of myopathy or malignant hyperthermia, normal basic blood chemistry and thyroid function, normal electrodiagnostic studies, normal or nonspecific muscle biopsy changes, and normal dystrophin immunohistochemistry. Of these 42, 4 each were excluded because their muscle tissue was no longer available for further analysis, or because reduced calpain-3 was found on Western blot, leaving 34 subjects with the possibility of IH. Laboratory information was available on relatives for 28 of these 34, with 13 families demonstrating designated hyperCKemia (FIH) in at least one member, thus constituting the substance of this report.

Mean age among FIH cases was 37 ± 3.4 years. Men were found to have hyperCKemia more often than women. Few subjects complained of muscle pain or fatigue (n = 5; 12%). Neurological examination was reportedly normal in all. Maximum CK ranged from 1.2-7.7 times the upper limit of normal. Among 12 patients seen 2-8 years after initial biopsy, examination and needle electromyography remained normal, and CK was unchanged. Calveolin-3 mutations were not found in 5 families studied. FIH is benign and, in 60% of patients, is autosomal dominant with a high male penetrance.

Commentary

Aggressive evaluation of what otherwise appears clinically to be benign hyperCKemia will yield a probable or definitive diagnosis in the majority. Among 104 asymptomatic (n = 50) or minimally symptomatic (n = 54, muscle pain, cramps, fatigue) patients with elevated creatine kinase (> 500 UI/L) and no muscle weakness, muscle biopsy revealed a diagnosis in 55% (Neurology. 2006;66:1585-1587). Glycogen storage diseases, muscular dystrophies, and inflammatory myopathy were the most frequent diagnoses, and diagnosis was more likely in children with higher CK levels. When in doubt, don't give up!