Trip Answers

Question answered:30/04/08

We searched the TRIP and Medline databases and the Lab Tests Online website but found no robust information to answer this question.

 

However, we did locate an article discussing macro CK as a rare but important cause of a raised serum creatine concentration that may be of relevance.

 

Galarraga et al state:

 

“Macroenzymes are enzymes with higher molecular mass than the corresponding enzyme normally found in serum. Several macroenzymes have been reported, the most common being macro CK (two types), macro amylase, macro lactate dehydrogenase and macro aspartate transaminase. All except macro CK type 2 consist of a normal enzyme complexed with an immunoglobulin, most commonly IgG or IgA. The complexed enzyme has reduced blood clearance, resulting in increased circulating amounts of the higher-than-normal molecular weight form of the relevant enzyme. When quantitative total CK assays are used, macro CK is indistinguishable from normal CK, causing an elevation of the total CK. Macroenzymes should be suspected when the enzyme levels are persistently raised with relatively constant levels and there is no obvious clinical explanation or other laboratory abnormality.”  [1]

 

In addition, we found several articles in Medline discussing idiopathic hyperCKemia that may be of relevance. Klein presents a case of hyperCKemia:

 

“A previously healthy 45-year-old woman presented with sudden onset of pain in her right leg, which began when she was washing her kitchen floor. She described the pain as starting from the knee and radiating to her hip. The pain progressed to the point that walking was difficult. No abnormalities were found during neurologic examination.
Results of radiographic investigations, including x-ray examination of her lumbar spine, hip, and pelvis and venous Doppler ultrasonography, were normal. Thyroid and parathyroid hormone levels were normal, as were electrolyte levels. The only abnormal finding was elevated creatine kinase at 841 U/L without elevation of the CK-MB fraction. Over the next few weeks, the patient’s leg pain gradually improved. Two years later, her symptom had not returned, but her serum CK remained elevated. Results of muscle biopsy were normal, and referral for genetic testing was suggested.”

 

The full text of this article can be read by following the link given in the references section below [2]. In the conclusion, Klein states:

 

“Elevated levels of CK occur frequently in family medicine. This article describes an approach to random elevated CK levels. Patients with elevated serum CK levels should undergo thorough initial investigation to determine common and potentially treatable causes of hyperCKemia. If no cause for an elevated CK level is found, the diagnosis of exclusion is IH. This relatively rare condition has been associated with malignant hyperthermia susceptibility and carrier status for DD. After the diagnosis of IH has been confirmed, patients can be reassured that clinical deterioration is rare.” [2]

 

Prelle et al presented the findings of a retrospectibe study of patients with asymptomatic or minimally raised serum creatine kinase levels. The abstract of this study reads:

 

“A retrospective evaluation of asymptomatic subjects with persistent elevation of serum creatine kinase (CK) levels (hyperCKemia) was made in order to verify the presence of subclinical myopathy or idiopathic hyperCKemia and to define the most appropriate diagnostic pathway. Persistently increased serum CK levels are occasionally encountered in healthy individuals. In 1980 Rowland coined for them the term idiopathic hyperCKemia. Despite the increase of scientific knowledge, several healthy subjects with hyperCKemia still represent a problem for the clinician.

 

We made a retrospective evaluation of 114 asymptomatic or minimally symptomatic individuals with incidentally detected persistent hyperCKemia. They underwent neurological examination and laboratory/instrumental evaluation. Skeletal muscle biopsy was performed and thoroughly investigated. Biochemical and genetic investigations were added in selected cases. Logistic regression analysis was applied. We diagnosed a neuromuscular disorder in 21 patients (18.4%), and found, by muscle biopsy and/or EMG, pathological but not conclusive findings in 57 subjects (50%). The statistic correlation between elevated serum CK levels and the probability of making a diagnosis changed according to the age of the patient. Conclusions: Muscle biopsy is the basic tool for screening asymptomatic subjects with hyperCKemia. It allowed us to make a diagnosis of disease in 18.4% of patients, and to detect skeletal muscle abnormalities in 38.6% of the subjects. Interestingly, 31.6% of individuals had completely normal muscle findings. These best fit the "diagnosis" of idiopathic hyperCKemia.” [3]

 

D’Adda et al reported on a followup to the Prelle et al study referred to above:

 

“Six years before the present study we performed a retrospective study of 114 subjects presenting with asymptomatic/ oligosymptomatic hyperckemia (raised creatine kinase blood levels), a diagnosis being made in 21 of them. We now present the results of a long-term follow-up in 55 of the still undiagnosed 93 individuals. Most of them have remained asymptomatic and did not develop specific neuromuscular disorders. One subject became frankly symptomatic manifesting limb-girdle weakness. A diagnosis of dystrophinopathy carrier and one of possible type I SMA carrier were indirectly made in another two subjects. Almost all subjects still have hyperckemia, though the mean creatine kinase (CK) value is lower than before. CK levels have become normal in 12 subjects. Two died of neoplasia, and six developed non-neuromuscular disorders. We noted no follow-up differences in terms of CK modifications between subjects with pathological EMG and/or muscle biopsy findings and those with normal findings at first examination.” [4]

 

References
1. Galarraga B, Sinclair D and Fahie-Wilson MN. A rare but important cause for a raised serum creatine kinase concentration: two case reports and a literature review. Rheumatology (Oxford). 2003 Jan;42(1):186-8. (http://rheumatology.oxfordjournals.org/cgi/content/full/42/1/186)
2. Klein D. Case report: hyperCKemia: a diagnostic dilemma. Can Fam Physician. 2005 Feb;51:240-1. (http://www.hubmed.org/display.cgi?uids=15751568)
3. Prelle A, Tancredi L, Sciacco M et al. Retrospective study of a large population of patients with asymptomatic or minimally symptomatic raised serum creatine kinase levels. J Neurol. 2002 Mar;249(3):305-11. (http://www.hubmed.org/display.cgi?uids=11993531)
4. D'Adda E, Sciacco M, Fruguglietti ME et al. Follow-up of a large population of asymptomatic/oligosymptomatic hyperckemic subjects. J Neurol. 2006 Nov ; 253(11): 1399-403. (http://www.hubmed.org/display.cgi?uids=16773272)

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