doi: 10.1161/01.CIR.0000012626.81324.38
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;105:1407.)
© 2002 American Heart Association, Inc.
Prevalence of Anderson-Fabry Disease in Male Patients With Late Onset Hypertrophic Cardiomyopathy
From the Department of Cardiological Sciences, St Georges Hospital Medical School, London, UK (B.S., W.J.M., P.M.E.); the First Department of Internal Medicine, Kagoshima University, Kagoshima, Japan (T.T., H.T., C.T.); and the Metabolic Unit, University College London Hospitals, London, UK (P.L.).
Correspondence to Dr P.M. Elliott, Department of Cardiological Sciences, St George’s Hospital Medical School, Cranmer Terrace, London, SW17 0RE, United Kingdom. E-mail pelliott{at}sghms.ac.uk
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background— Although studies have suggested that "late-onset" hypertrophic cardiomyopathy (HCM) may be caused by sarcomeric protein gene mutations, the cause of HCM in the majority of patients is unknown. This study determined the prevalence of a potentially treatable cause of hypertrophy, Anderson-Fabry disease, in a HCM referral population.
Methods and Results— Plasma 
-galactosidase A (-Gal) was measured in 79 men with HCM who were diagnosed at 
40 years of age (52.9±7.7 years; range, 40–71 years) and in 74 men who were diagnosed at <40 years (25.9±9.2 years; range, 8–39 years). Five patients (6.3%) with late-onset disease and 1 patient (1.4%) diagnosed at <40 years had low -Gal activity. Of these 6 patients, 3 had angina, 4 were in New York Heart Association class 2, 5 had palpitations, and 2 had a history of syncope. Hypertrophy was concentric in 5 patients and asymmetric in 1 patient. One patient had left ventricular outflow tract obstruction. All patients with low -Gal activity had -Gal gene mutations.
Conclusion— Anderson-Fabry disease should be considered in all cases of unexplained hypertrophy. Its recognition is important given the advent of specific replacement enzyme therapy.
Key Words: Anderson-Fabry disease • cardiomyopathy • hypertrophy
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Hypertrophic cardiomyopathy (HCM) is defined by the presence of unexplained myocardial hypertrophy. In the majority of patients, the disease is caused by autosomal-dominant inherited mutations in 1 of 9 genes that encode different cardiac sarcomeric proteins.1 In 1995, Nakao and colleagues2 reported a 3% prevalence of Anderson-Fabry disease in predominantly middle-aged male patients with left ventricular hypertrophy (LVH) associated with diverse pathologies. The implication of their study was that this now-treatable disease is frequently undiagnosed. The aim of the present study was to determine the prevalence of Anderson-Fabry disease in a referral population of male patients with a clinical diagnosis of HCM.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patients
The study cohort was composed of 79 consecutive men with HCM who were first diagnosed at
40 years of age (mean, 52.9±7.7 years; range, 40 to 71 years). A total of 74 men diagnosed at <40 years of age (mean, 25.9±9.2 years; range, 8 to 39 years) were studied for comparison. All had apparently unexplained LVH with a maximum left ventricular wall thickness 13 mm. Clinical examination, supine 12-lead electrocardiography, and ambulatory 48-hour ECG monitoring were performed in all patients. M-mode, 2D, and Doppler echocardiography were performed as previously described3 using a GE System V echocardiograph. The severity and distribution of LVH were assessed in the parasternal short-axis plane at the mitral valve and papillary muscle level. Maximum left ventricular wall thickness was defined as the greatest thickness in any single segment. Patterns of hypertrophy were defined in accordance with previously published methods.3 Maximal left ventricular outflow tract flow velocity was determined using continuous-wave Doppler, and pressure gradients were calculated using the simplified Bernoulli equation. Left ventricular inflow velocities were obtained from the apical 4-chamber view using pulsed-wave Doppler echocardiography.
Screening for Anderson-Fabry Disease
Plasma -galactosidase A (-Gal) activity was measured with the fluorogenic substrate 4-methylumbelliferyl--D-galactopyranoside (Sigma), with N-acetyl-D-galactosamine (Nacalai Tesque) used as an inhibitor of -N-acetylgalactosaminidase as described previously.2 On the basis of previously published data, a plasma -Gal activity of <1.2 nmol · h–1 · mL–1 was considered diagnostic of Anderson-Fabry disease.2 Plasma -Gal activity in 89 normal healthy men (aged 52±19 years; range, 14 to 80 years) was also measured.
Genetic Analysis
Mutations in the -Gal gene were identified by amplifying each exon using polymerase chain reaction, followed by single-strand conformation polymorphism analysis (SSCP) and direct sequencing. Intronic oligonucleotide primers were designed using the PRIMER program (HGMP resource center, MRC Clinical Research Center). An ammonium acetate salting-out procedure was used to isolate genomic DNA from whole blood, as described previously.4 Both polymerase chain reaction and SSCP analysis were performed using previously described methods.5 All samples demonstrating an SSCP variation were directly sequenced using Dynal bead (Dynal) DNA strand separation and the Sequenase II kit (USB).4
Statistical Analysis
The 
2 test was used to compare noncontinuous variables, and the 2-tailed unpaired t test was used to compare continuous variables. Statistical significance was defined as P<0.05.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Baseline clinical data are summarized in Table 1. A total of 5 of 79 patients (6.3%) diagnosed at
40 years and 1 of 74 patients (1.4%) diagnosed at <40 years had low -Gal activity (range 0.1 to 0.7 nmol · h–1 · mL–1). -Gal activity in the remaining 147 patients was 7.4±2.7 nmol · h–1 · mL–1 (range, 2.3 to 25.0 nmol · h–1 · mL–1). Plasma -Gal activity in the 89 controls was 8.4±2.4 nmol · h–1 · mL–1 (range, 4.8 to 17.6 nmol · h–1 · mL–1). All 6 patients with low -Gal activity had cardiovascular symptoms at presentation. None had a family history of cardiomyopathy or Anderson-Fabry disease. All were normotensive, and 2 had an elevated serum creatinine. Retrospective clinical examination revealed angiokeratoma and acroparaesthesia in 1 patient (patient 3). Five of the 6 patients had undergone coronary angiography; 4 had angiographically normal coronary arteries, and one had a 50% stenosis in the circumflex artery (patient 1).
|
All 6 patients with low -Gal activity had an abnormal ECG (Table 2 and Figure 1). One patient (patient 6) had been paced for symptomatic second-degree heart block and was in atrial fibrillation. The ECGs in the remaining 5 patients all met Romhilt-Estes6 criteria for LVH. Two patients had one or more episodes of nonsustained ventricular tachycardia during Holter monitoring.
|
|
The echocardiographic features in the patients with Anderson-Fabry disease are shown in Table 3. Maximum left ventricular wall thickness was 21±4 mm (range, 14–26 mm). Five had concentric hypertrophy (Figure 2), and one had asymmetric septal hypertrophy (patient 6). One patient had systolic anterior motion of the mitral valve and a left ventricular outflow tract gradient of 80 mm Hg (patient 4).
|
|
Genetic Analysis
Patients 1, 4, and 5 had the same missense mutation in exon 5 (an adenine to guanine transition at position 644, leading to the substitution of serine for asparagine at residue 215). Patient 2 had a novel thymidine-to-cytosine transition at position 950 in exon 6, resulting in the substitution of threonine for isoleucine at residue 317. Patient 6 had a guanine-to-thymidine transition at nucleotide 937 in exon 6 of the coding sequence, which predicted a substitution of tyrosine for aspartic acid at residue 313. Patient 3 had a novel single base pair deletion at position 1223, predicting a frameshift in the reading frame at amino acid 408 and premature termination of translation of the protein product.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Clinical features of Anderson-Fabry disease usually appear in childhood and adolescence. As patients age, cardiovascular disease, including conduction abnormalities, cardiomyopathy, and stroke, become a major cause of morbidity.7 Several reports have suggested that some male hemizygotes remain asymptomatic for most of their adult life. In a study of 1603 men undergoing echocardiography, Nakao and colleagues2 identified 230 individuals with a left ventricular wall thickness of at least 13 mm, of whom 7 (3%) had
-Gal deficiency. Notably, 6 of the 7 were said to have unexplained hypertrophy. The wider significance of these findings was, however, uncertain because the prevalence of unexplained hypertrophy was unusually high (3% compared with estimates of between 1/500 and 1/1000 in most population studies).8
Comparison of Anderson-Fabry Disease and Familial HCM
Most patients with familial HCM have asymmetrical septal hypertrophy (ASH).3 In contrast, 5 of the 6 patients with low -Gal activity in this study had concentric hypertrophy. These data are consistent with a recent study of 30 patients with Anderson-Fabry disease; 37% of these patients had concentric LVH, 10% had ASH, and 3% had an eccentric pattern of hypertrophy.9 In 25% of patients with familial HCM, ASH is associated with dynamic subaortic obstruction.10 In the present study, one patient with Anderson-Fabry disease had a typical outflow gradient in association with concentric hypertrophy.
Many electrocardiographic abnormalities have been described in Anderson-Fabry disease, including short PR intervals and prolonged QRS duration. Both are also described in familial HCM.11 With regard to arrhythmia, one patient with low -Gal activity had permanent atrial fibrillation and 2 had nonsustained ventricular tachycardia on Holter monitoring. The prevalence and clinical significance of these arrhythmias in Anderson-Fabry disease cannot, however, be determined from the present study.
Clinical Implications
The present study demonstrates that, as a cause for HCM, Anderson-Fabry disease is at least as common as some sarcomeric protein gene mutations.1 It should be suspected in male patients with concentric hypertrophy and no family history of HCM or inheritance consistent with X-linked disease. Correct diagnosis is important because recent advances in the treatment of Anderson-Fabry disease may offer stabilization and reversal of some cardiovascular manifestations.12,13
Limitations
In view of the X-linked recessive inheritance of Anderson-Fabry disease, we only screened male patients. Although female heterozygotes can also present with cardiac involvement, biochemical diagnosis can be problematic because they often have intermediate levels of enzyme activity overlapping with those seen in normal controls.
The normal controls in this study were Japanese. Although this raises the possibility of ethnic differences, the -Gal levels used to define Anderson-Fabry disease conform with those used in Western populations.
Received December 18, 2001; revision received January 29, 2002; accepted January 29, 2002.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Spirito P, Seidman CE, Mckenna WJ, et al. The management of hypertrophic cardiomyopathy. N Engl J Med. 1997; 336: 775–785.
2.
Nakao S, Takenaka T, Maeda M, et al. An atypical variant of Fabry’s disease in men with left ventricular hypertrophy. N Engl J Med. 1995; 333: 288–293.
3. Maron BJ, Gottdiener JS, Epstein SE. Patterns and significance of distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy: a wide angle two-dimensional echocardiographic study of 125 patients. Am J Cardiol. 1981; 48: 418–428.[CrossRef][Medline] [Order article via Infotrieve]
4.
Davies JP, Winchester BG, Malcolm S. Sequence variations in the first exon of alpha-galactosidase A. J Med Genet. 1993; 30: 658–663.
5.
Davies JP, Winchester BG, Malcolm S. Mutational analysis in patients with the typical form of Anderson-Fabry disease. Hum Mol Genet. 1993; 2: 1051–1053.
6. Romhilt DW, Estes EH Jr. A point-score system for the ECG diagnosis of left ventricular hypertrophy. Am Heart J. 1968; 75: 752–758.[CrossRef][Medline] [Order article via Infotrieve]
7.
Desnick RJ, Ioannou YA, Eng CM. -Galactosidase, a deficiency: Fabry disease. In: Scriver CR, Beaudet AL, Sly WS, et al, eds. The Metabolic and Molecular Basis of Inherited Disease. 7th ed. Vol 2. New York: McGraw-Hill; 1995: 2741–2784.
8.
Maron BJ, Gardin JM, Flack JM, et al. Prevalence of hypertrophic cardiomyopathy in a general population of young adults: echocardiographic analysis of 4111 subjects in the CARDIA Study. Circulation. 1995; 92: 785–789.
9. Linhart A, Palecek T, Bultas J, et al. New insights in cardiac structural changes in patients with Fabry’s disease. Am Heart J. 2000; 139: 1101–1108.[CrossRef][Medline] [Order article via Infotrieve]
10. Wigle ED, Sasson Z, Henderson MA, et al. Hypertrophic cardiomyopathy: the importance of the site and extent of hypertrophy: a review. Prog Cardiovasc Dis. 1985; 28: 1–83.[CrossRef][Medline] [Order article via Infotrieve]
11.
Savage DD, Seides SF, Clark CE, et al. Electrocardiographic findings in patients with obstructive and non-obstructive hypertrophic cardiomyopathy. Circulation. 1978; 58: 402–409.
12.
Schiffmann R, Kopp JB, Austin HA3rd, et al. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA. 2001; 285: 2743–2749.
13.
Eng CM, Guffon N, Wilcox WR, et al, for the International Collaborative Fabry Disease Study Group. Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry’s disease. N Engl J Med. 2001; 345: 9–16.
This article has been cited by other articles:
 |
|
 |
|
  T. D. Karamitsos, J. M. Francis, S. Myerson, J. B. Selvanayagam, and S. Neubauer The Role of Cardiovascular Magnetic Resonance Imaging in Heart Failure J. Am. Coll. Cardiol., October 6, 2009; 54(15): 1407 - 1424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-Y. Lin, K.-W. Chong, J.-H. Hsu, H.-C. Yu, C.-C. Shih, C.-H. Huang, S.-J. Lin, C.-H. Chen, C.-C. Chiang, H.-J. Ho, et al. High Incidence of the Cardiac Variant of Fabry Disease Revealed by Newborn Screening in the Taiwan Chinese Population Circ Cardiovasc Genet, October 1, 2009; 2(5): 450 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ghio, M. Revera, F. Mori, C. Klersy, A. Raisaro, C. Raineri, A. Serio, M. Pasotti, and L. O. Visconti Regional abnormalities of myocardial deformation in patients with hypertrophic cardiomyopathy: correlations with delayed enhancement in cardiac magnetic resonance Eur J Heart Fail, October 1, 2009; 11(10): 952 - 957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Mehta, J T R Clarke, R Giugliani, P Elliott, A Linhart, M Beck, G Sunder-Plassmann, and on behalf of the FOS Investigators Natural course of Fabry disease: changing pattern of causes of death in FOS - Fabry Outcome Survey J. Med. Genet., August 1, 2009; 46(8): 548 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Oqvist, B. M. Brenner, J. P. Oliveira, A. Ortiz, R. Schaefer, E. Svarstad, C. Wanner, K. Zhang, and D. G. Warnock Nephropathy in Fabry disease: the importance of early diagnosis and testing in high-risk populations Nephrol. Dial. Transplant., June 1, 2009; 24(6): 1736 - 1743. [Full Text] [PDF]
|
|
|
|
 |
|
 B. L. Thurberg, J. T. Fallon, R. Mitchell, T. Aretz, R. E. Gordon, and M. W. O'Callaghan Cardiac Microvascular Pathology in Fabry Disease: Evaluation of Endomyocardial Biopsies Before and After Enzyme Replacement Therapy Circulation, May 19, 2009; 119(19): 2561 - 2567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Hershberger, J. Cowan, A. Morales, and J. D. Siegfried Progress With Genetic Cardiomyopathies: Screening, Counseling, and Testing in Dilated, Hypertrophic, and Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Circ Heart Fail, May 1, 2009; 2(3): 253 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. De Cobelli, A. Esposito, E. Belloni, M. Pieroni, G. Perseghin, C. Chimenti, A. Frustaci, and A. Del Maschio Delayed-Enhanced Cardiac MRI for Differentiation of Fabry's Disease from Symmetric Hypertrophic Cardiomyopathy Am. J. Roentgenol., March 1, 2009; 192(3): W97 - W102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. M. Hess, W. McKenna, and H.-P. Schultheiss CHAPTER 18 Myocardial Disease ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Schoenmakere, B. Poppe, B. Wuyts, K. Claes, D. Cassiman, B. Maes, D. Verbeelen, R. Vanholder, D. R. Kuypers, N. Lameire, et al. Two-tier approach for the detection of alpha-galactosidase A deficiency in kidney transplant recipients Nephrol. Dial. Transplant., December 1, 2008; 23(12): 4044 - 4048. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Joshi, W. Ahmar, G. Lee, and A. Aggarwal Fabry's disease presenting as ventricular tachycardia and Left Ventricular 'Hypertrophy' Eur J Echocardiogr, September 1, 2008; 9(5): 697 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Chimenti, N. Hamdani, N. M. Boontje, F. DeCobelli, A. Esposito, J. G.F. Bronzwaer, G. J.M. Stienen, M. A. Russo, W. J. Paulus, A. Frustaci, et al. Myofilament Degradation and Dysfunction of Human Cardiomyocytes in Fabry Disease Am. J. Pathol., June 1, 2008; 172(6): 1482 - 1490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kounas, C. Demetrescu, A. A. Pantazis, A. Keren, P. J. Lee, D. Hughes, A. Mehta, and P. M. Elliott The Binary Endocardial Appearance Is a Poor Discriminator of Anderson-Fabry Disease From Familial Hypertrophic Cardiomyopathy J. Am. Coll. Cardiol., May 27, 2008; 51(21): 2058 - 2061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D A Hughes, P M Elliott, J Shah, J Zuckerman, G Coghlan, J Brookes, and A B Mehta Effects of enzyme replacement therapy on the cardiomyopathy of Anderson Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa Heart, February 1, 2008; 94(2): 153 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Terryn, B. Poppe, B. Wuyts, K. Claes, B. Maes, D. Verbeelen, R. Vanholder, K. De Boeck, N. Lameire, A. De Paepe, et al. Two-tier approach for the detection of alpha-galactosidase A deficiency in a predominantly female haemodialysis population Nephrol. Dial. Transplant., January 1, 2008; 23(1): 294 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Andrade, P. J. Waters, R. S. Singh, A. Levin, B.-C. Toh, H. D. Vallance, and S. Sirrs Screening for Fabry Disease in Patients with Chronic Kidney Disease: Limitations of Plasma {alpha}-Galactosidase Assay as a Screening Test Clin. J. Am. Soc. Nephrol., January 1, 2008; 3(1): 139 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Monserrat, J. R. Gimeno-Blanes, F. Marin, M. Hermida-Prieto, A. Garcia-Honrubia, I. Perez, X. Fernandez, R. de Nicolas, G. de la Morena, E. Paya, et al. Prevalence of Fabry Disease in a Cohort of 508 Unrelated Patients With Hypertrophic Cardiomyopathy J. Am. Coll. Cardiol., December 18, 2007; 50(25): 2399 - 2403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Hansen and N. Merchant MRI of Hypertrophic Cardiomyopathy: Part 2, Differential Diagnosis, Risk Stratification, and Posttreatment MRI Appearances Am. J. Roentgenol., December 1, 2007; 189(6): 1344 - 1352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. H. Robin, P. B. Tabereaux, R. Benza, and B. R. Korf Genetic Testing in Cardiovascular Disease J. Am. Coll. Cardiol., August 21, 2007; 50(8): 727 - 737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Marian Phenotypic Plasticity of Sarcomeric Protein Mutations J. Am. Coll. Cardiol., June 26, 2007; 49(25): 2427 - 2429. [Full Text] [PDF]
|
|
|
|
|
|
A. Linhart and P. M Elliott The heart in Anderson-Fabry disease and other lysosomal storage disorders Heart, April 1, 2007; 93(4): 528 - 535. [Full Text] [PDF]
|
|
|
|
|
|
S. D. Colan, S. E. Lipshultz, A. M. Lowe, L. A. Sleeper, J. Messere, G. F. Cox, P. R. Lurie, E. J. Orav, and J. A. Towbin Epidemiology and Cause-Specific Outcome of Hypertrophic Cardiomyopathy in Children: Findings From the Pediatric Cardiomyopathy Registry Circulation, February 13, 2007; 115(6): 773 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Schiffmann Enzyme Replacement in Fabry Disease: The Essence Is in the Kidney Ann Intern Med, January 16, 2007; 146(2): 142 - 144. [Full Text] [PDF]
|
|
|
|
|
|
Developed in Collaboration With the European Heart, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al. ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) J. Am. Coll. Cardiol., September 5, 2006; 48(5): e247 - e346. [Full Text] [PDF]
|
|
|
|
 |
|
 Writing Committee Members, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Europace, September 1, 2006; 8(9): 746 - 837. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Parkinson-Lawrence, M. Fuller, J. J. Hopwood, P. J. Meikle, and D. A. Brooks Immunochemistry of Lysosomal Storage Disorders Clin. Chem., September 1, 2006; 52(9): 1660 - 1668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Morita, M. G. Larson, S. C. Barr, R. S. Vasan, C. J. O'Donnell, J. N. Hirschhorn, D. Levy, D. Corey, C. E. Seidman, J.G. Seidman, et al. Single-Gene Mutations and Increased Left Ventricular Wall Thickness in the Community: The Framingham Heart Study Circulation, June 13, 2006; 113(23): 2697 - 2705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Pieroni, C. Chimenti, F. De Cobelli, E. Morgante, A. Del Maschio, C. Gaudio, M. A. Russo, and A. Frustaci Fabry's Disease Cardiomyopathy: Echocardiographic Detection of Endomyocardial Glycosphingolipid Compartmentalization J. Am. Coll. Cardiol., April 18, 2006; 47(8): 1663 - 1671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P M Elliott, H Kindler, J S Shah, B Sachdev, O E Rimoldi, R Thaman, M T Tome, W J McKenna, P Lee, and P G Camici Coronary microvascular dysfunction in male patients with Anderson-Fabry disease and the effect of treatment with {alpha} galactosidase A Heart, March 1, 2006; 92(3): 357 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yang, C. J. McMahon, L. R. Smith, J. Bersola, A. M. Adesina, J. P. Breinholt, D. L. Kearney, W. J. Dreyer, S. W. Denfield, J. F. Price, et al. Danon Disease as an Underrecognized Cause of Hypertrophic Cardiomyopathy in Children Circulation, September 13, 2005; 112(11): 1612 - 1617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Mahrholdt, A. Wagner, R. M. Judd, U. Sechtem, and R. J. Kim Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies Eur. Heart J., August 1, 2005; 26(15): 1461 - 1474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Van Driest, S. R. Ommen, A. J. Tajik, B. J. Gersh, and M. J. Ackerman Yield of Genetic Testing in Hypertrophic Cardiomyopathy Mayo Clin. Proc., June 1, 2005; 80(6): 739 - 744. [Abstract] [PDF]
|
|
|
|
|
|
R. T. Murphy, J. Mogensen, K. McGarry, A. Bahl, A. Evans, E. Osman, P. Syrris, G. Gorman, M. Farrell, J. L. Holton, et al. Adenosine monophosphate-activated protein kinase disease mimicks hypertrophic cardiomyopathy and Wolff-Parkinson-White syndrome: Natural history J. Am. Coll. Cardiol., March 15, 2005; 45(6): 922 - 930. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Arad, B. J. Maron, J. M. Gorham, W. H. Johnson Jr., J. P. Saul, A. R. Perez-Atayde, P. Spirito, G. B. Wright, R. J. Kanter, C. E. Seidman, et al. Glycogen Storage Diseases Presenting as Hypertrophic Cardiomyopathy N. Engl. J. Med., January 27, 2005; 352(4): 362 - 372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Chimenti, M. Pieroni, E. Morgante, D. Antuzzi, A. Russo, M. A. Russo, A. Maseri, and A. Frustaci Prevalence of Fabry Disease in Female Patients With Late-Onset Hypertrophic Cardiomyopathy Circulation, August 31, 2004; 110(9): 1047 - 1053. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P Charron, E Villard, P Sebillon, P Laforet, T Maisonobe, L Duboscq-Bidot, N Romero, V Drouin-Garraud, T Frebourg, P Richard, et al. Danon's disease as a cause of hypertrophic cardiomyopathy: a systematic survey Heart, August 1, 2004; 90(8): 842 - 846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C.C. Moon, B. Sachdev, A. G. Elkington, W. J. McKenna, A. Mehta, D. J. Pennell, P. J. Leed, and P. M. Elliott Gadolinium enhanced cardiovascular magnetic resonance in Anderson-Fabry disease: Evidence for a disease specific abnormality of the myocardial interstitium Eur. Heart J., December 1, 2003; 24(23): 2151 - 2155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Maron, W. J. McKenna, G. K. Danielson, L. J. Kappenberger, H. J. Kuhn, C. E. Seidman, P. M. Shah, W. H. Spencer III, P. Spirito, F. J. Ten Cate, et al. American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1687 - 1713. [Full Text] [PDF]
|
|
|
|
|
|
Writing Committee Members, B. J. Maron, W. J. McKenna, G. K. Danielson, L. J. Kappenberger, H. J. Kuhn, C. E. Seidman, P. M. Shah, W. H. Spencer III, P. Spirito, et al. American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy: A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines Eur. Heart J., November 1, 2003; 24(21): 1965 - 1991. [Full Text] [PDF]
|
|
|
|
 |
|
 A. B Mehta, S. Lewis, and C. Laverey Treatment of lysosomal storage disorders BMJ, August 30, 2003; 327(7413): 462 - 463. [Full Text] [PDF]
|
|
|
|
|
|
S F Nagueh Fabry disease Heart, August 1, 2003; 89(8): 819 - 820. [Full Text] [PDF]
|
|
|
|
|
|
S R Ommen, R A Nishimura, and W D Edwards Fabry disease: a mimic for obstructive hypertrophic cardiomyopathy? Heart, August 1, 2003; 89(8): 929 - 930. [Full Text] [PDF]
|
|
|
|
|
|
A Morrone, C Cavicchi, T Bardelli, D Antuzzi, R Parini, M Di Rocco, S Feriozzi, O Gabrielli, R Barone, G Pistone, et al. Fabry disease: molecular studies in Italian patients and X inactivation analysis in manifesting carriers J. Med. Genet., August 1, 2003; 40(8): e103 - 103. [Full Text] [PDF]
|
|
|
|
|
|
J Mogensen, A Bahl, T Kubo, N Elanko, R Taylor, and W J McKenna Comparison of fluorescent SSCP and denaturing HPLC analysis with direct sequencing for mutation screening in hypertrophic cardiomyopathy J. Med. Genet., May 1, 2003; 40(5): e59 - 59. [Full Text] [PDF]
|
|
|
|
|
|
M. Pieroni, C. Chimenti, R. Ricci, P. Sale, M. A. Russo, and A. Frustaci Early Detection of Fabry Cardiomyopathy by Tissue Doppler Imaging Circulation, April 22, 2003; 107(15): 1978 - 1984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Mogensen, A. Bahl, and W. J McKenna Hypertrophic cardiomyopathy--the clinical challenge of managing a hereditary heart condition Eur. Heart J., March 2, 2003; 24(6): 496 - 498. [Full Text] [PDF]
|
|
|
|
|
|
R. J. Desnick, R. Brady, J. Barranger, A. J. Collins, D. P. Germain, M. Goldman, G. Grabowski, S. Packman, and W. R. Wilcox Fabry Disease, an Under-Recognized Multisystemic Disorder: Expert Recommendations for Diagnosis, Management, and Enzyme Replacement Therapy Ann Intern Med, February 18, 2003; 138(4): 338 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Breunig and C. Wanner Enzyme replacement therapy for Fabry disease: proving the clinical benefit Nephrol. Dial. Transplant., January 1, 2003; 18(1): 7 - 9. [Full Text] [PDF]
|
|
|
|
|
|
J. P. Veinot, P.M. Elliott, B. Sachdev, W.J. McKenna, T. Takenaka, H. Teraguchi, C. Tei, and P. Lee Prevalence of Anderson-Fabry Disease in Male Patients With Late Onset Hypertrophic Cardiomyopathy * Response Circulation, October 8, 2002; 106 (15): e73 - e73. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Arad, J.G. Seidman, and C. E. Seidman Phenotypic diversity in hypertrophic cardiomyopathy Hum. Mol. Genet., October 1, 2002; 11(20): 2499 - 2506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. MEHTA New developments in the management of Anderson-Fabry disease QJM, October 1, 2002; 95(10): 647 - 653. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||