Familial idiopathic hyper‐CK‐emia: An underrecognized condition

Abstract

Persistent elevation of serum creatine kinase (CK) in individuals with normal neurological and laboratory examinations has been called idiopathic hyperCKemia (IH). IH has been reported in rare families and was recently ascribed to caveolin-3 gene mutations. We retrospectively found that IH was familial in 13 of 28 subjects in whom serum CK was measured in relatives. These 13 families had a total of 41 subjects with IH, including six over 60 years of age. In eight families there was male-to-male transmission and a higher prevalence of males with hyperCKemia. Muscle biopsy in one member of all families was normal or showed minimal, nonspecific changes. Morphometric examination disclosed different patterns of changes in fiber size and distribution. Caveolin-3 expression was normal and in five families molecular genetics excluded caveolin-3 gene mutations. Our findings suggest that IH is familial in 46% of cases. Familial IH is a benign genetically heterogeneous condition that is autosomal-dominant in at least 60% of cases, with a higher penetrance in men.

Approach to asymptomatic creatine kinase elevation

“…In one study, 37 elevated CK was found in family members of 13 of 28 unrelated probands. In the 13 families, 41 individuals had elevated CK.…”

ACASQ1founder mutation in three Italian families with protein aggregate myopathy and hyperCKaemia

“…Familial idiopathic hyperCKaemia is a benign genetically heterogeneous condition, with autosomal dominant features in a high proportion of cases and higher penetrance in males 5. Although many of these patients have been extensively investigated, the genetic defect underlying the hyperCKaemia has been identified in only a small number of cases.…”

Malignant hyperthermia

“…Persistently elevated serum concentration of creatine kinase (CK) usually accompanies muscle weakness in patients with myopathies. However, it may also be found in individuals with a normal neurological examination, possibly due to subclinical or preclinical neuromuscular disorders, dystrophinopathy carrier state, hypothyroidism, hypoparathyroidism, alcoholism, or intake of statins and other drugs, and this condition is labeled asymptomatic hyperCKemia [78-80]. When the cause is not found, even after extensive investigations, the condition is defined as IH.…”

“…When the cause is not found, even after extensive investigations, the condition is defined as IH. Capasso et al [80] studied a series of individuals with IH and found IH is familial in 46% of cases and familial IH is a benign genetically heterogeneous condition that is autosomal-dominant in at least 60% of cases, with higher penetrance in men.…”