CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 1, February 2012
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which was consistent with chronic renal failure. An antinuclear
antibody test done to rule out a connective tissue disorder was
negative. Thyroid function tests were normal. Lipid profile showed
a borderline increase in total cholesterol (5.27 mmol/l) and low-
density lipoprotein cholesterol (3.64 mmol/l) for which drug
therapy, which was previously lacking, was initiated. The patient
had an HbA
1c
level of 10.2%.
The patient was discharged home on regular follow up.
Discussion
Serum total CK activity and that of its isoenzymes is a frequently
requested test that is used as an indicator of injuries to the skel-
etal muscle and myocardium. While the use of troponin assays
has largely superseded that of CK-MB for the evaluation of
acute coronary syndromes, many centres in Kenya still rely on
CK-MB.
In our laboratory, creatine kinase MB isoenzyme activity is
determined using an immuno-inhibition method on an Olympus
AU600 automated analyser. Immuno-inhibition is one of several
methods that can be used for measuring CK-MB. It is a simple,
rapid and automated method using polyclonal anti-human anti-
bodies to human CK-M subunit that inhibits CK-M. Residual
CK activity representing CK-B subunit activity is doubled to
obtain CK-MB activity. A number of limitations of this method
exist, one of which includes presence of CK-BB or other CK
variant forms, which contribute to uninhibited CK activity,
falsely elevating levels of CK-MB. In such cases, correction of
results is required and electrophoresis can be used.
8
Our two cases were from patients older than 50 years and both
genders. Macro CK type 1 has been shown to occur in healthy
individuals
9
and is most commonly found in women and patients
over the age of 50 years.
6
There are several reported associations
of this enzyme with disease states, including hypothyroidism,
neoplasia, autoimmune disease, myositis, gastrointestinal disease
and cardiovascular disease.
4,10
As mentioned earlier, macro CK
type 1 is created via an antigen–antibody reaction.
Both our patients suffered from coronary artery disease and
uncontrolled hypertension. A study done in Spain investigating a
series of patients with macro CK type 1 showed that three of the
total seven patients had confirmed cardiovascular pathology.
11
While the elevated total CK and CK-MB activity in both
patients were partly attributable to cardiac origin, clinical situ-
ations may be encountered where CK-MB elevation is non-
cardiac in origin in a patient suspected to have an acute coronary
syndrome. The difficulty lies in detecting macro CK in patients
who present with an acute myocardial infarction and the pres-
ence of macro CK. Reported cases of macro CK are usually in
patients with normal troponin I or troponin T levels.
Case reports in the literature show patients with macro CK
and negative troponin levels.
12,13
Both our cases initially had
elevated troponin I and CK-MB in their clinical course, which
could be attributed to their cardiac pathology; cardiomyopathy
and acute myocardial infarction, respectively. Detecting macro
CK in patients with cardiac pathology, who are known to have
elevated CK-MB, poses a great challenge. Our patient with
an acute myocardial infarction had both an elevated CK-MB and
troponin I on the day of admission but subsequently, troponin
I levels normalised and CK-MB levels were found to be higher
than total CK.
Our first patient was diagnosed with GBS, which is a known
cause of myopathy. A study done by Hsiao
et al
. showed that
macro CK type 1 occurred predominantly in patients with
myopathy and hypothesised that CK might become antigenic
after cellular destruction.
10
Our second patient had ulcerative colitis. A study done in
patients with inflammatory bowel disease found that macro CK
type 1 was present in 16.7% of patients with ulcerative colitis.
12
Another study in Switzerland showed presence of macro CK
type 1 in a patient with ulcerative colitis.
13
Conclusion
A number of studies have shown that macro CK type 1 is of no
pathological significance, although this remains controversial
and requires further clarification.
1-3,14,15
It can result in diagnostic
confusion and may lead to unnecessary investigations, inappro-
priate treatment and anxiety for both the patient and the clini-
cian.
16
In addition, it poses a difficulty in following up patients
who are on statins.
17
Neither of our patients was on statins.
Therefore, it is imperative that the cause of falsely elevated
CK-MB isoenzyme be identified.
References
1. Sturk A, Sanders GT. Macro enzymes: prevalence, composition, detec-
tion and clinical relevance.
J Clin Chem Clin Biochem
1990;
28
(2):
65–81.
2. Galasso PJ, Litin SC, O’Brien JF. The macroenzymes: a clinical review.
Mayo Clin Proc
1993;
68
(4): 349–354.
3. Miffin TE, Bruns DE. University of Virginia case conference:
Macroamylase, macro creatine kinase and other macroenzymes.
Clin
Chem
1985;
31
: 1743–1748.
4. Galarraga B, Sinclair D, Fahie-Wilson MN, McCrae FC, Hull RG,
Ledingham JM. A rare but important cause for a raised serum crea-
tine kinase concentration: two case reports and a literature review.
Rheumatology (Oxford)
2003;
42
(1): 186–188.
5. Kyung N, Lee GC, Bernhard P, Elin RJ. Relevance of macro creatine
kinase type 1 and type 2 lsoenzymes to laboratory and clinical data.
Clin Chem
1994;
40
(7): 1278–1283.
6. Wu AH, Herson VC, Bowers GN, Jr. Macro creatine kinase types 1
and 2: clinical significance in neonates and children as compared with
adults.
Clin Chem
1983;
29
(1): 201–204.
7. Schmid H, Muhlbayer D, Roling J, Sternfeld T, Julg B, Schlattner U,
et
al
. Macroenzyme creatine kinase (CK) type 2 in HIV-infected patients
is significantly associated with TDF and consists of ubiquitous mito-
chondrial CK.
Antivir Ther
2006;
11
(8): 1071–1080.
8. Morison IM, Clayson KJ, Fine JS. Effect of creatine kinase-MM
subtype composition on a CK-MB immunoinhibition assay.
Clin Chem
1988;
34
(3): 535–538.
9. Whelan PV Malkus H. A macro CK isoenzyme in serum of apparently
healthy individuals.
Clin Chem
1983;
29
: 1411–1414.
10. Hsiao JF, Ning HC, Gu PW, Lin WY, Chu PH. Clinical role of recur-
rently elevated macro creatine kinase type 1.
J Clin Lab Anal
2008;
22
(3): 186–191.
11. Rosa-Jimenez F, Gasso de Campos M, Camacho Reina MV, Vazquez
de Castroviejo E, Hernandez Burruezo JJ, Pousibet Sanfeliu H. [Macro
creatine kinase type 1 as a cause of increase of CF-MB isoenzyme.
Apropos of 7 cases].
Rev Esp Cardiol
1997;
50
(3): 166–172.
12. Perez-Calle JL, Marin-Jimenez I, Lopez-Serrano P, Gisbert JP, Pena
AS, Fernandez-Rodriguez C. Prevalence of macrocreatinkinase type 1
in patients with inflammatory bowel disease.
Dig Dis Sci
2008;
53
(2):
486–489.
13. Z’Graggen WJ, Wehrli C, Gautschi K, Alex V, Conen D. [Differential
diagnostic considerations in CK-MB level increase].
Praxis
(Bern
1994) 2000;
89
(45): 1864–1867.
