Key Clinical Message
Common diagnostic approach in patients with suspected cardiac
amyloidosis includes cardiac magnetic resonance imaging and
scintigraphy. We report the first clinical case of false positive
results of scintigraphy in a patient with Danon disease.
Introduction
We report a clinical case of a patient who had a hypertrophic
cardiomyopathy of unknown etiology. We used variety of tests among which
were cardiac magnetic resonance imaging (CMR) and scintigraphy. CMR
showed dubious results but scintigraphy was false positive. As we know,
there were no reports of scintigraphy false positive results indicating
cardiac amyloidosis.
Case report
A 23‐year‐old man presented with leg edema, ascites, shortness of
breath, history of intermittent palpitations and syncope, mild proximal
muscle weakness and cognitive deficit. The patient reported that his
mother died suddenly at the age of 22 years. Heart failure symptoms
progressively worsened from the age of 16 years. He was earlier
diagnosed with asymmetric non-obstructive hypertrophic cardiomyopathy,
WPW-syndrome, and complete left bundle-branch block. He used metoprolol
25 mg a day and irregularly torasemide without medical monitoring.
Laboratory tests revealed increased levels of creatine kinase, lactate
dehydrogenase, aspartate aminotransferase, alanine aminotransferase
which was believed to be caused by myopathy. Moreover, electromyography
of the deltoid muscle showed the typical myopathic pattern.
CMR showed left and right ventricle hypertrophy (interventricular septum
thickness of 24 mm), interventricular asynchrony, and dilation of the
pulmonary arteries and the inferior vena cava. Late gadolinium
enhancement (LGE) imaging showed early subendocardial LGE throughout all
LV segments which is not typical for HCM and amyloidosis.
Considering patient’s young age, family history, and the absence of
kidney involvement and polyneuropathy, the most probable diagnosis
seemed to be a glycogen storage disease. ATTR amyloidosis was included
in differential diagnosis.
Further we performed scintigraphy and rectal mucosal biopsy. Bone tracer
cardiac scintigraphy using 99mTc-labeled pyrophosphate showed cardiac
uptake consistent with ATTR amyloidosis. However, amyloid deposits were
not found in biopsy specimens. Heart muscle biopsy was not performed due
to high perioperative risks.
The definitive diagnosis was established after genetic tests. We found a
frameshifting mutation in LAPM2 gene which means that patient had Danon
disease.
Unfortunately, there is no specific treatment available for this
disorder. The patient received implantable cardioverter defibrillator
considering the high risk of sudden cardiac death. Symptomatic treatment
included furosemide and spironolactone.
Discussion
Genetic disorders including metabolic diseases are reported to account
for up to 10 % of all causes of hypertrophic cardiomyopathy1. It is easy to suspect one in cases like ours
however definitive diagnosis may be difficult to establish.
Our patient had features of metabolic disease: young age, family
history, proximal muscle involvement, and cognitive deficit.
Interestingly, our patient had WPW-syndrome — another common feature
of a storage disease 1. Particularly, the whole
picture was rather typical for a Danon disease. Danon disease is
lysosome-associated membrane protein 2 (LAMP2) deficiency characterized
by severe cardiomyopathy, mild skeletal myopathy, ophthalmic
abnormalities, and variable intellectual disability2.
Interesting part of our case is that after dubious results of contrast
enhance MRI, cardiac scintigraphy showed false positive results
indicating cardiac amyloidosis. It is important to note that these
modalities are a part of a common diagnostic algorithm3. To our knowledge, there were no reports of a case
like ours. These modalities are believed to be highly specific but one
should remember of rare conditions which could mimic cardiac
amyloidosis.
Author Contribution
DA: wrote and revised manuscript. DS: wrote and revised manuscript. TR:
revised manuscript. EM: revised manuscript and figure acquisition. OL
revised manuscript and figure acquisition. SP: revised manuscript. EZ:
revised manuscript. VS: revised manuscript. SM: revised manuscript.
Conflict of interest
None declared.
References:
1. Task A, Elliott PM, Uk C, et al. 2014 ESC Guidelines on diagnosis and
management of hypertrophic cardiomyopathy The Task Force for the
Diagnosis and Management of Hypertrophic Cardiomyopathy of the European
Society of Cardiology ( ESC ). 2014:2733-2779.
doi:10.1093/eurheartj/ehu284
2. Arad M, Maron BJ, Gorham JM, et al. Glycogen storage diseases
presenting as hypertrophic cardiomyopathy. N Engl J Med .
2005;352(4):362-372. doi:10.1056/NEJMoa033349
3. Dorbala S, Ando Y, Bokhari S, et al. EXPERT CONSENSUS
RECOMMENDATIONS. J Nucl Cardiol . 2019.
doi:10.1007/s12350-019-01761-5
Figure 1. CMR. 4 chamber view reveals myocardial hypertrophy up to 24 mm
mostly in the interventricular segments (square), right side hydrothorax
(asterisk), mild pericardial effusion (two asterisks).
Figure 2. Post-contrast images demonstrate subendocardial LGE in all LV
segments. This pattern of LGE is not typical for HCM and amyloidosis.