Description

A man in his 70s with no other significant medical history presented with a 2 month history of dyspnoea on exertion. He was the eighth of ten siblings and had a remarkable family history for heart diseases: his mother, oldest brother and seventh oldest sister had died of heart failure. Physical examination revealed a mild peripheral oedema without any murmur or crackles. He denied any muscle pain. An ECG revealed a sinus rhythm with low voltage complexes and a pseudoinfarct pattern. Chest radiography showed cardiomegaly without pleural effusion. His echocardiogram indicated a left ventricular ejection fraction of 42%, thickening of the ventricular walls and an impaired diastolic function. Laboratory findings showed an elevation of creatine kinase (CK) of 823 U/L (normal, 59–248 U/L), CK-MB of 9.5 ng/mL (normal, <5.2 ng/mL), troponin I of 55.4 pg/mL (normal, <34.2 pg/mL) and N-terminal pro-brain natriuretic peptide (NT-proBNP) of 1162 pg/mL (normal, <125 pg/mL). Of note, his CK level 1 year prior to this visit had also been elevated (402 U/L). Further investigation of electrophoresis of CK isoenzyme revealed a macro-CK type 1 (figure 1). Coronary angiography showed no significant stenoses in the coronary vessels. Blood and urinary immunoelectrophoresis analyses and a serum nephelometric assay of the light chain were all negative. However, ^99mTc-pyrophosphate (PYP) scintigraphy demonstrated diffuse intense ^99mTc-PYP uptake in the heart. A myocardial biopsy specimen demonstrated amyloid deposits with Congo red staining (figure 2A). In addition, an immunoenzymatic staining was positive with a horseradish peroxidase labelled antitransthyretin antibody (figure 2B). Therefore, we confirmed a diagnosis of amyloid transthyretin (ATTR) amyloidosis.

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Figure 1

Electrophoresis of creatine kinase (CK) isoenzyme revealing a macro-CK type 1 (arrow).

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Figure 2

(A) A myocardial biopsy specimen showing amyloid deposits with Congo red staining. (B) An immunohistochemistry specimen showing positive staining with a horseradish peroxidase labelled antitransthyretin antibody. Scale bar = 100 µm.

Previous studies have reported a staging system for ATTR amyloidosis using an NT-proBNP, high sensitivity troponin or estimated glomerular filtration rate.1 Although the association with cardiac amyloidosis and troponin has been established, the relationship between ATTR amyloidosis and CK remains unknown.2 3 The typical CK isoenzymes include CK-BB, CK-MB and CK-MM, whereas macro-CK type 1 is an atypical CK enzyme with a higher molecular mass. Macro-CK type 1 is an enzyme-antibody complex formed by one of the CK isoenzymes and immunoglobulins. As its molecular weight is slightly different from these isoenzymes, macro-CK type 1 migrates between CK-MM and CK-MB on electrophoresis of CK isoenzymes.4 Although there is no well-established association of a particular disease with macro-CK type 1, it has been reportedly associated with a variety of diseases such as hypothyroidism, malignancies, autoimmune diseases, myositis, irritable bowel syndrome and bronchopulmonary chronic illness.5

To the best of our knowledge, this is the first reported case of a coexisting ATTR amyloidosis and macro-CK type 1. The deposition of transthyretin might potentially explain the formation of an immune complex, but further investigations will be needed to see whether macro-CK type 1 is associated with ATTR amyloidosis.