the evaluation of hypertrophic cardiomyopathy ( hcm ) involves the careful exclusion of diseases that can cause increased left ventricular wall thickness , such as aortic stenosis , poorly controlled hypertension , and infiltrative processes such as cardiac amyloidosis and sarcoidosis . fabry disease , an inherited deficiency of the enzyme -galactosidase a , is a rare cause of left ventricular hypertrophy , especially , has drawn much attention for nearly curative treatments.1 ) exogenous administration of the deficient enzyme has been shown to clear microvascular endothelial deposits , which are essential to disease manifestation , in the kidney , skin , and heart . in one study , this enzyme deficiency is found in 10% of male subjects with myocardial hypertrophy without definite cause.2 ) whereas another study showed that approximately 6% of men and 12% of women with late - onset hcm actually had evidence of fabry disease.3 ) if this storage disease is misdiagnosed as hcm , patients who could be treated effectively with medication might be subjected to aggressive procedures such as septal ablation or surgical septal myectomy . we report a case of fabry disease which presented with hcm and tricuspid regurgitation and underwent an open heart surgery . a 71-year - old female presented with dyspnea ( new york heart association functional class iii ) and severe edema on both legs on july 2015 . in 1999 , she was diagnosed with non - obstructive hcm , and her symptom was stationary until january 2015 when her dyspnea and peripheral edema were aggravated and referred to our hospital . routine hematologic tests showed iron deficiency anemia ( hemoglobin : 9.7 g / dl ) and normal coagulation profile . chemical profile was within normal range including normal renal function ( blood urea nitrogen / cr : 11/0.84 mg / dl ) . chest x - ray revealed a marked cardiomegaly ( cardiothoracic ratio = 84% ) . a 12-lead electrocardiogram ( ecg ) showed atrial fibrillation with a mean ventricular rate of 56 bpm and st - t change ( fig . 1 ) . echocardiography showed a markedly thickened wall of left ventricle and right ventricle with a high echo density and severe tricuspid regurgitation ( fig . 2 ) . cardiac magnetic resonance image showed a fuzzy delayed gadolinium enhancement at the mid anterolateral and inferolateral myocardium of the left ventricle suggestive of infiltrative diseases such as amyloidosis and sarcoidosis ( fig . hematoxylin and eosin staining showed a diffuse vacuolization of myocytes and lateralization of nucleus ( fig . congo - red staining was negative and no definite sarcoid granuloma or amorphous amyloid deposition was identified , which excluded the possibility of cardiac sarcoidosis or amyloidosis . therefore , initial pathologic diagnosis was vacuolar change of myocyte . for the management of her symptom , cardiac surgery including tricuspid annuloplasty , maze operation and right atrial reduction plasty was performed . after surgery , her symptom was improved to mild exertional dyspnea ( new york heart association functional class i  ii ) and the edema on both legs decreased . on echocardiography , tricuspid regurgitation was reduced to mild to moderate and a moderate resting pulmonary hypertension was noted with a maximal velocity of tricuspid regurgitation of 3.5 m / sec . during follow - up after cardiac surgery , a plasma -galactosidase activity was checked for the screening of fabry disease . dna analysis was implemented for confirmation and it revealed a heterozygote -galactosidase mutation at exon 6 [ c.901c > t ( p.arg301ter ) ] ( fig . 5 ) . since teenager , she had pain on the palms and soles ( acroparesthesia ) , hypohidrosis and a heat and cold intolerance . 6 ) , and conjunctival vascular tortuosity . no retinal vascular tortuosity was found on fundoscopic examination . the albumin / creatinine ratio ( 141.4 mg / day , reference range : 0100 mg / day ) and the amount of 24-hour urine protein ( 7837.0 mg / g , reference range : 030 mg / g ) were increased . she started to be treated with enzyme replacement therapy ( ert ) using -galactosidase . on the family screening , her younger sister and her first son were turned out to be affected by fabry disease . her first son who was 44 years old had acroparesthesia on hands and feet and hypohidrosis since he was 9 years old . his proteinuria and abnormal ecg were detected since 2014 , and left ventricular hypertrophy was observed on his echocardiographic examination . fabry disease is a x - linked recessive metabolic disorder characterized by deficient activity of the lysosomal hydrolase , -galactosidase a.4 ) this enzymatic defect leads to the progressive accumulation of glycosphingolipids , predominantly globotriaosylceramide ( gb3 ) , within the lysosomes of endothelial cells . the clinical manifestations depend on the part of body which is damaged , and acroparesthesias , hypohidrosis , corneal opacities ( cornea verticillata ) and dysfunction of the kidney , brain , and heart can be developed.5 ) cardiac manifestation can be seen in almost all patients , but symptoms from the cardiovascular system appear much later than gb3 accumulation starts . the mean age of cardiac symptom onset is 32 years and 40 years in male and female patients , respectively . the cardiovascular complications include myocardial hypertrophy of the left ventricle , thickening of the valves , dilatation of the ascending aorta and conduction disturbances . 6 ) in the end stage of cardiomyopathy caused by fabry disease , myocardial fibrosis is extensive , and systolic and diastolic left ventricular functions become severely impaired.7 ) in our case , a severe ventricular hypertrophy was developed , which might resulted in atrial fibrillation and tricuspid regurgitation . myocardial echo density was very high , resembling the typical feature of myocardial sparkling found in cardiac amyloidosis . however , ecg did not show a low voltage which is typically caused by interstitial infiltration of amyloid , and amyloid infiltration was not found in myocardial biopsy . fabry disease cardiomyopathy mimics hcm and infiltrative disease in respect to the morphologic and clinical features . therefore , differential diagnosis is not easy and frequently relies on invasive studies such as endomyocardial biopsy or molecular and gene analysis . in particular , fabry disease cardiomyopathy shares many clinical and morphologic features with hcm , and fabry disease can not be differentiated if we do not suspect and pay attention to systemic manifestations of this disease . however , some clues of fabry disease can be found in heart . on echocardiography , patients with hcm show more frequently present with asymmetric septal hypertrophy and outflow tract pressure gradient in comparison with patients with fabry disease . a binary appearance of left ventricular endocardial border , reflecting the endocardial and subendocardial compartmentalization of glycosphingolipid material , can be a good indicator of fabry cardiomyopathy.8 ) tissue doppler imaging , and strain rate imaging can help to detect early diastolic dysfunction due to regional fibrosis in fabry disease.9)10 ) cardiac magnetic resonance has no pathognomic finding of fabry disease , but the difference of focal late enhancement pattern can be helpful . in most fabry disease patients ( 92% ) , late gadolinium enhancement was noted in the basal infero - lateral walls.11 ) in fabry cardiomyopathy , endomyocardial biopsy shows cardiomyocytes containing large perinuclear and cytoplasmic vacuoles representing accumulation of glycolipid material and the characteristic appearance of lamellar bodies inclusion in electron microscopy,12 ) whereas hcm shows only disarrayed hypertrophied myocytes without cytoplasmic vacuoles . the diagnosis of fabry disease starts from clinical suspicion . if there are 2 or more clinical problems among acroparesthesia or neuritic pain in hands or feet , persistent proteinuria of unknown cause , progressive renal impairment of obscure cause , unexplained hcm , angiokeratomas etc . , high suspicion of fabry disease should be raised , then galactosidase a activity assays should be checked for screening . in affected males , enzyme assays usually show severely diminished activity in plasma and leukocytes and fabry disease diagnosis can be confirmed without further exam . however enzyme activity in heterozygote female is usually normal as in our case , confirmation exam such as detection of a gene mutation or tissue biopsy is needed , if the patient is suspicious of fabry disease . after a fabry disease - specific gene mutation is identified or cytoplasmic vacuoles in light microcopy or lamellar bodies inclusion in electron microscopy on biopsy tissue is noted , fabry disease can be confirmed . all family members suspected of having fabry disease should be tested , even if they have no symptoms . patients with unexplained left ventricular hypertrophy should be checked if they have symptoms related to fabry disease . ert stabilizes the levels of gb3 in the endothelial cells of the myocardium leading to reduce fibrosis development , and consequently improves left ventricular function.13 ) however , the treatment is effective when the disease 's state is early and myocardial fibrosis is in a low degree.14 ) regarding other systems , treatment reduces neuropathic pain , stabilizes renal function and contributes to the regression of the major pathological complications as well as to an improvement in prognosis . our case was not diagnosed with fabry disease until cardiac surgery was performed to correct severe tricuspid regurgitation and atrial fibrillation . if fabry disease was confirmed earlier and ert was started , ventricular hypertrophy might be regressed before cardiac surgery was required .
a 71-year - old female who was diagnosed with nonobstructive hypertrophic cardiomyopathy since 1999 presented with dyspnea and severe edema on both legs . for the management of her symptom , cardiac surgery including tricuspid annuloplasty , maze operation and right atrial reduction plasty was performed . during follow - up after cardiac surgery 
 , a plasma -galactosidase activity was checked for the screening of fabry disease and the result was around lower normal limit . 
 dna analysis was implemented for confirmation and it revealed a heterozygote -galactosidase mutation at exon 6 [ c.901c > t ( p.arg301ter ) ] . 
 this case suggests that fabry disease might be easily undetected , and clinical suspicion is critical .