Effectiveness of agalsidase alfa enzyme replacement in Fabry disease: cardiac outcomes after 10 years’ treatment
© Kampmann et al. 2016
Received: 4 May 2015
Accepted: 6 September 2015
Published: 29 September 2015
To explore long-term effects of agalsidase alfa on Fabry disease cardiomyopathy in adults.
Retrospective analysis of prospectively collected data at a single center in Mainz, Germany, revealed that 45 adult patients (21 men, 24 women) had received agalsidase alfa for approximately 10 years. Data were extracted for cardiac and heart failure status, echocardiographic evaluations of cardiac structure and function, and renal function at treatment start and during agalsidase alfa treatment.
After 10 years of agalsidase alfa treatment, heart failure classification had improved by at least 1 class in 22/42 patients, and angina scores were stable or improved in 41/42 patients. During treatment, no patients without left ventricular hypertrophy (LVH) at treatment initiation developed LVH, and no patients with LVH at treatment initiation showed a decline in left ventricular mass.
Approximately 10 years of agalsidase alfa treatment appeared to have beneficial effects for controlling progression and improving some symptoms of Fabry-associated cardiomyopathy.
KeywordsAgalsidase alfa Cardiomyopathy Enzyme replacement therapy Fabry disease Left ventricular hypertrophy Lysosomal storage disorder
Fabry disease is a rare, inherited, X-chromosome linked glycosphingolipid storage disorder (OMIM 301500). In Fabry disease, mutations in the α-galactosidase A (GLA) gene cause functional deficiency of the enzyme α-GLA. In affected patients, lack of α-GLA activity leads to progressive accumulation of glycosphingolipids, particularly globotriaosylceramide (Gb3), in lysosomes, affecting almost all tissues and organs. By adulthood, patients with Fabry disease may experience a range of serious complications, such as cardiomyopathy, that result in significant morbidity and reduced life expectancy [1–10]. Because the GLA gene is located on the X-chromosome, males generally tend to be more severely affected than females, as the latter retain a physiologically significant level of enzyme α-GLA activity. Symptom onset in females, therefore, generally occurs later in life, with cardiomyopathy the most common and serious sign .
Cardiac changes in Fabry disease include progressive, infiltrative hypertrophic cardiomyopathy characterized by predominantly left ventricular (LV) wall thickening without cavity dilatation, structural changes in the mitral and aortic valves, and conduction abnormalities that may lead to increased susceptibility to arrhythmias [7–15]. The severity of cardiac symptoms correlates with overall disease progression over time, with intracellular deposition of Gb3 and fibrosis thought to be major, but not the only, mechanisms underlying these abnormalities [7, 8, 16–18].
Agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease has been available for more than 10 years [19–23]. A number of studies of different designs support the efficacy and effectiveness of ERT, including agalsidase alfa, with regard to cardiac outcomes in adults [13, 21–27]. Reports of other studies, however, have suggested that ERT with either agalsidase alfa or beta may be less effective in patients with disease of longer duration and more severe symptoms at ERT initiation or that findings are equivocal [28–30].
To establish a clear understanding of the long-term effectiveness of agalsidase alfa in preventing and controlling the progression of cardiomyopathy in Fabry disease, we conducted a 10-year retrospective medical record review-based evaluation of morphological and functional cardiac changes in adult men and women treated with agalsidase alfa.
Study design and patients
A single-center retrospective analysis was carried out using prospectively collected data extracted from the medical records of patients with Fabry disease who were under the care of the University Children’s Hospital in Mainz, Germany, which is a participating center in the Fabry Outcome Survey (sponsored by Shire). Predefined data were extracted from medical records after written consent from patients and after local institutional review board and ethical committee approval of this analysis. Eligible patients had a Fabry disease diagnosis confirmed by enzyme assay (males) and/or DNA analysis (males and females), were aged ≥ 14 years at treatment start, and had received agalsidase alfa (Replagal®; Shire, Lexington, Massachusetts, USA) ERT for approximately 10 years.
All eligible patients received ERT continuously and none had ERT withdrawn or stopped. Female patients with intermittent reimbursement from the health care system were excluded from this analysis and 4 female patients were excluded because ERT was stopped for more than a year.
Demographic characteristics and disease-related clinical parameters at the start of treatment were collected. Data were extracted for cardiac and heart failure status, echocardiographic evaluations of cardiac structure and function, and renal function at treatment start and then at predefined time points during agalsidase alfa treatment.
Heart failure and angina were evaluated as New York Heart Association (NYHA) classification of heart failure and Canadian Cardiovascular Society (CCS) grading of angina pectoris scores, respectively [30–32]. Detailed echocardiography was performed using digital echocardiographic equipment with appropriate transducers. Mean values were taken from instantaneous measurements made over 3 cardiac cycles from M-mode tracings according to American Society of Echocardiography recommendations . Systolic and diastolic structural and functional parameters were calculated as described elsewhere [9, 14, 34]. LV mean wall thickness (MWT) measurements of ≥16 mm were considered to indicate severe LV hypertrophy (LVH) . LV mass was calculated from echocardiographic measurement data and values indexed to patient height (LV mass index [LVMI]) . Values of >50 g/m2.7 were considered indicative of LVH . Systolic function was evaluated from LV ejection fraction (LVEF) measured using two-dimensional echocardiography [7, 9, 14, 37].
Renal function was evaluated from serum creatinine; estimated glomerular filtration rate (eGFR), calculated as eGFR Modification of Diet in Renal Disease values;  and time-averaged urinary protein excretion.
Descriptive statistics were calculated for all values. Changes from baseline in study parameters were evaluated as changes in least squares (LS) mean values over time with 95 % confidence intervals (CI) adjusted for baseline demographic variables, or by calculating t statistic values. Differences were considered statically significant if p - values were ≤0.05. SAS/STAT® software version 9.2 (SAS Institute Inc., Cary, North Carolina, USA) was used for statistical analyses.
Demographic and basic clinical parameters at treatment start
Age, mean (SD), years
Age at ERT start, mean (SD), years
Age at ERT start, median (range), years
BMI, mean (SD), kg/m2
Systolic BP, mean (SD), mmHg
Diastolic BP, mean (SD), mmHg
Heart rate, mean (SD), bpm
Diabetes, n (%)
Current smoker, n (%)
Arterial hypertension, n (%)
Concomitant therapies included: percutaneous transluminal coronary angioplasty in 2 patients; placement of a dual chamber pacemaker in 3 patients; dialysis in 1 patient who had progressed to end-stage renal disease; and beta-adrenergic blocking agents in 1 patient. In addition, all patients initiated therapy with angiotensin-converting enzyme inhibitors during the first 5 years of ERT. No patients received cardiac resynchronization therapy or an automatic implantable cardioverter defibrillator.
NYHA classifications and CCS scores
Cardiac structural evaluations
Before ERT, mean (SD) MWT values for males (12.3 [2.9] mm; n = 21) and females (11.7 [2.5] mm; n = 24) indicated mild hypertrophy, although values ranged from normal to some instances of severe LVH (range, males 8.2–18.0 mm; females 8.7–17.0 mm). After 10 years of treatment, MWT was significantly reduced in males (LS mean [95 % CI] change −1.89 [−2.58, −1.19] mm; p < 0.0001), with changes apparent after 1 year (−2.08 [−2.69, −1.46] mm; p < 0.0001). Statistically significant changes were also apparent after 1 year in females (LS mean [95 % CI] change −2.01 [−2.55, −1.47] mm; p < 0.0001), although after 10 years, MWT was not significantly different from before treatment (−0.48 [−1.05, 0.09] mm; p = 0.0999).
Cardiac functional evaluations
Changes in left ventricular ejection fraction functional parameter, after approximately 10 years of agalsidase alfa treatment
Left ventricular ejection fraction (%)
Baseline, mean (SD)
71.9 (7.6), n = 23
69.9 (7.3), n = 21
10-year n, mean (SD)
Change from baselinea
−3.64 (−6.74, −0.54)
1.31 (−2.16, 4.78)
p = 0.022
This study represents one of the largest and longest-term evaluations to date of the progression of cardiomyopathy in patients with Fabry disease who received 10 years of agalsidase alfa ERT.
The progression of untreated Fabry disease differs in some respects in men and women as a result of differences in levels of residual enzyme activity [3, 39–42]. Additionally, the differential cardiac effects in men and women may be caused by a mosaic distribution of affected and unaffected cardiac myocytes in women [2, 43]. Although symptoms appear approximately 10 years earlier in males, cardiac involvement is now understood to be prevalent in adult patients of both genders [2, 9, 15], with reports of ≥90 % of patients being affected by cardiomyopathy, with LVH in about half of untreated men and one third of untreated women, and >50 % of female patients reporting chest pain [13, 39–41]. The severity of cardiac abnormalities increases with age and, alongside renal disease, are a significant cause of morbidity and early mortality in both genders [2, 3, 7–10, 12, 13, 15, 39–41, 44]. A study of Fabry disease in 36 women (mean [SD] age, 47.0 [17.9] years) found that 25 (69 %) had LVH at baseline; after 4 years of agalsidase alfa ERT, there was significant reduction in LVMI in 22/25 (88 %) patients who had LVH at baseline, with 7/25 (28 %) no longer classified as having LVH . Further, among those women with LVMI classified as normal at baseline, only 1 had progressed to LVH after 4 years of ERT .
One of the goals for ERT should be the prevention of future organ damage in patients who are not yet severely affected at the time of diagnosis, but who may develop symptoms later in their lives without treatment. It should also be noted that some patients will not develop progressive symptoms even without treatment and thus will have little or no benefit from treatment. The patient cohort presented here consists of classical Fabry patients with typical signs and symptoms of Fabry disease who still show excellent responses to treatment. However, despite the beneficial effects of ERT in patients with Fabry disease, patients in advanced stages of the disease may still die. From an analysis of deceased patients of our overall center cohort who have not been included in the analysis presented here due to their shorter treatment time (data not shown), no obvious overall demographic or Fabry disease-related differences were noted between those patients who died during the observation period and our patient cohort in total, except for the fact that more deceased patients were male and older at treatment initiation. Therefore, these non-responders may have been primarily those patients in whom ERT was initiated too late.
Our analysis included men and women with Fabry disease who had received agalsidase alfa for approximately 10 years. Improvements in NYHA heart failure classification and CCS angina scores were observed over this period. From a structural perspective, early improvements in MWT in male and female patients were observed, although there were no significant differences at 10 years. Also, LVMI values in the normal range before treatment were maintained over 10 years in men and women. Where LVH was present before ERT, improvements were apparent after just 1 year, with benefits in male patients sustained after 10 years and with deterioration controlled in females. Cardiac functionality parameters were stable over the 10-year study period, as evidenced by maintenance of LVEF values within the normal range. Electrocardiographic data are not presented because they do not reflect limited changes in LV mass and typically do not detect changes seen during ERT. Renal function was also generally maintained after 10 years of ERT. While differences are apparent in some of the 10-year analysis results between men and women, possibly because of the more severe effects of Fabry disease in men, we found that disease progression was generally attenuated and symptoms of cardiomyopathy were stable or improved in male and female patients who received 10 years of ERT.
A number of studies and analyses have explored the effects of agalsidase alfa on cardiomyopathy in Fabry disease over shorter time frames. Over treatment duration periods from 6 months to 5 years, agalsidase alfa has been reported to delay the onset of cardiac involvement, to reduce or stabilize LVMI in men and women with Fabry disease, and to reduce myocardial Gb3 in males [21–26]. Specifically, in patients with signs of LVH before ERT, decreases in LVMI over 1 to 5 years of treatment have been reported, whereas in patients without initial LVH, 3 to 5 years of treatment prevented progression [21, 23, 24]. Functionally, increased or stabilized mid-wall fractional shortening after 5 years of treatment regardless of baseline LVH has been reported , with no LVEF changes found in male patients after 6 months’ treatment in another study . The findings of our retrospective analysis are thus in accord with those of previous studies of treatment over shorter time periods and further indicate the potential benefits of agalsidase alfa. Our results suggest that agalsidase alfa has long-term benefits for Fabry disease cardiomyopathy regardless of gender and of the severity of cardiac symptoms before treatment.
This was a retrospective analysis of data from medical records and not a prospective randomized controlled trial. Hence, patients were not randomly selected to receive ERT and the analysis did not include a comparator (control) group of untreated patients. Comparisons with pre-treatment data were therefore used to evaluate changes in parameters. As these baseline data were collected 10 years previously, the treated patients may have been considerably older when the comparisons were made, and aging itself may have had an adverse impact on the symptoms evaluated. Although M-mode echocardiography has inherent limitations of variability and reproducibility, and thus is not the ideal method for serial measurement of LVMI, it is widely available and commonly used. Finally, patients whose data were included had been referred for specialist treatment and, in the case of the female patients, severe disease was more likely.
In this 10-year evaluation of adult men and women with Fabry disease who received agalsidase alfa treatment, there was no progression of cardiomyopathy as determined by a range of structural and functional parameters.
Left ventricular hypertrophy
Enzyme replacement therapy
New York Heart Association
Canadian Cardiovascular Society
Mean wall thickness
LV ejection fraction
estimated glomerular filtration rate
Left ventricular mass index
We thank all patients who consented to the inclusion of their clinical data in this analysis. We also would like to thank Dr. Nesrin Karabul, Dr. Leila Arash-Kaps, Dr. Catharina Whybra, Dr. Eugen Mengel, Dr. J. Reinke, and the whole team of the Villa Metabolica for their help and support. Medical writing assistance during the preparation of this manuscript, supported financially by Shire, was provided by Annie Rowe and Margit Rezabek of Excel Scientific Solutions.
Statement of authorship
The authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Mehta A, Clarke JT, Giugliani R, Elliott P, Linhart A, Beck M, et al. Natural course of Fabry disease: changing pattern of causes of death in FOS - Fabry Outcome Survey. J Med Genet. 2009;46(8):548–52.View ArticlePubMedGoogle Scholar
- Kampmann C, Linhart A, Baehner F, Palecek T, Wiethoff CM, Miebach E, et al. Onset and progression of the Anderson-Fabry disease related cardiomyopathy. Int J Cardiol. 2008;130(3):367–73.View ArticlePubMedGoogle Scholar
- Schiffmann R, Warnock DG, Banikazemi M, Bultas J, Linthorst GE, Packman S, et al. Fabry disease: progression of nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement therapy. Nephrol Dial Transplant. 2009;24(7):2102–11.View ArticlePubMedPubMed CentralGoogle Scholar
- Sadick N, Thomas L. Cardiovascular manifestations in Fabry disease: a clinical and echocardiographic study. Heart Lung Circ. 2007;16(3):200–6.View ArticlePubMedGoogle Scholar
- Weidemann F, Breunig F, Beer M, Sandstede J, Stork S, Voelker W, et al. The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease. Eur Heart J. 2005;26(12):1221–7.View ArticlePubMedGoogle Scholar
- Mehta A, Ricci R, Widmer U, Dehout F, Garcia de Lorenzo A, Kampmann C, et al. Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur J Clin Invest. 2004;34(3):236–42.View ArticlePubMedGoogle Scholar
- Kampmann C, Baehner F, Ries M, Beck M. Cardiac involvement in Anderson-Fabry disease. J Am Soc Nephrol. 2002;13 Suppl 2:S147–9.PubMedGoogle Scholar
- Linhart A, Palecek T, Bultas J, Ferguson JJ, Hrudová J, Karetová D, et al. New insights in cardiac structural changes in patients with Fabry's disease. Am Heart J. 2000;139(6):1101–8.View ArticlePubMedGoogle Scholar
- Kampmann C, Baehner F, Whybra C, Martin C, Wiethoff CM, Ries M, et al. Cardiac manifestations of Anderson-Fabry disease in heterozygous females. J Am Coll Cardiol. 2002;40(9):1668–74.View ArticlePubMedGoogle Scholar
- Perrot A, Osterziel KJ, Beck M, Dietz R, Kampmann C. Fabry disease: focus on cardiac manifestations and molecular mechanisms. Herz. 2002;27(7):699–702.View ArticlePubMedGoogle Scholar
- Linhart A. The heart in Fabry disease. In: Mehta A, Beck M, Sunder-Plassmann G, editors. Fabry Disease: Perspectives from 5 Years of FOS. Oxford: Oxford PharmaGenesis; 2006. p. 189–201.Google Scholar
- Linhart A, Elliott PM. The heart in Anderson-Fabry disease and other lysosomal storage disorders. Heart. 2007;93(4):528–35.View ArticlePubMedPubMed CentralGoogle Scholar
- Linhart A, Kampmann C, Zamorano JL, Sunder-Plassmann G, Beck M, Mehta A, et al. Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey. Eur Heart J. 2007;28(10):1228–35.View ArticlePubMedGoogle Scholar
- Kampmann C, Wiethoff CM, Martin C, Wenzel A, Kampmann R, Whybra C, et al. Electrocardiographic signs of hypertrophy in Fabry disease-associated hypertrophic cardiomyopathy. Acta Paediatr Suppl. 2002;91 Suppl 439:21–7.View ArticlePubMedGoogle Scholar
- Shah JS, Hughes DA, Sachdev B, Tome M, Ward D, Lee P, et al. Prevalence and clinical significance of cardiac arrhythmia in Anderson-Fabry disease. Am J Cardiol. 2005;96(6):842–6.View ArticlePubMedGoogle Scholar
- Elleder M, Bradová V, Smíd F, Budĕsínský M, Harzer K, Kustermann-Kuhn B, et al. Cardiocyte storage and hypertrophy as a sole manifestation of Fabry's disease. Report on a case simulating hypertrophic non-obstructive cardiomyopathy. Virchows Arch A Pathol Anat Histopathol. 1990;417(5):449–55.View ArticlePubMedGoogle Scholar
- von Scheidt W, Eng CM, Fitzmaurice TF, Erdmann E, Hubner G, Olsen EG, et al. An atypical variant of Fabry's disease with manifestations confined to the myocardium. N Engl J Med. 1991;324(6):395–9.View ArticleGoogle Scholar
- Costanzo L, Buccheri S, Capranzano P, Di Pino L, Curatolo G, Rodolico M, et al. Early cardiovascular remodelling in Fabry disease. J Inherit Metab Dis. 2014;37(1):109–16.View ArticlePubMedGoogle Scholar
- Schiffmann R, Kopp JB, Austin 3rd HA, Sabnis S, Moore DF, Weibel T, et al. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA. 2001;285(21):2743–9.View ArticlePubMedGoogle Scholar
- Breunig F, Weidemann F, Strotmann J, Knoll A, Wanner C. Clinical benefit of enzyme replacement therapy in Fabry disease. Kidney Int. 2006;69(7):1216–21.View ArticlePubMedGoogle Scholar
- Mehta A, Beck M, Elliott P, Giugliani R, Linhart A, Sunder-Plassmann G, et al. Enzyme replacement therapy with agalsidase alfa in patients with Fabry's disease: an analysis of registry data. Lancet. 2009;374(9706):1986–96.View ArticlePubMedGoogle Scholar
- Hughes DA, Elliott PM, Shah J, Zuckerman J, Coghlan G, Brookes J, et al. Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa. Heart. 2008;94(2):153–8.View ArticlePubMedGoogle Scholar
- Beck M, Ricci R, Widmer U, Dehout F, de Lorenzo AG, Kampmann C, et al. Fabry disease: overall effects of agalsidase alfa treatment. Eur J Clin Invest. 2004;34(12):838–44.View ArticlePubMedGoogle Scholar
- Kampmann C, Linhart A, Devereux RB, Schiffmann R. Effect of agalsidase alfa replacement therapy on Fabry disease-related hypertrophic cardiomyopathy: a 12- to 36-month, retrospective, blinded echocardiographic pooled analysis. Clin Ther. 2009;31(9):1966–76.View ArticlePubMedGoogle Scholar
- Whybra C, Miebach E, Mengel E, Gal A, Baron K, Beck M, et al. A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease. Genet Med. 2009;11(6):441–9.View ArticlePubMedGoogle Scholar
- Zamorano J, Serra V, Peréz de Isla L, Feltes G, Calli A, Barbado FJ, et al. Usefulness of tissue Doppler on early detection of cardiac disease in Fabry patients and potential role of enzyme replacement therapy (ERT) for avoiding progression of disease. Eur J Echocardiogr. 2011;12(9):671–7.View ArticlePubMedGoogle Scholar
- Rombach SM, Smid BE, Linthorst GE, Dijkgraaf MG, Hollak CE. Natural course of Fabry disease and the effectiveness of enzyme replacement therapy: a systematic review and meta-analysis: effectiveness of ERT in different disease stages. J Inherit Metab Dis. 2014;37(3):341–52.View ArticlePubMedGoogle Scholar
- El Dib RP, Nascimento P, Pastores GM. Enzyme replacement therapy for Anderson-Fabry disease. Cochrane Database Syst Rev. 2013;2(Feb 28), CD006663.PubMedGoogle Scholar
- Weidemann F, Niemann M, Störk S, Breunig F, Beer M, Sommer C, et al. Long-term outcome of enzyme-replacement therapy in advanced Fabry disease: evidence for disease progression towards serious complications. J Intern Med. 2013;274(4):331–41.View ArticlePubMedPubMed CentralGoogle Scholar
- Weidemann F, Strotmann JM, Niemann M, Herrmann S, Wilke M, Beer M, et al. Heart valve involvement in Fabry cardiomyopathy. Ultrasound Med Biol. 2009;35(5):730–5.View ArticlePubMedGoogle Scholar
- American Heart Assocation. Classification of functional capacity and objective assessment. http://my.americanheart.org/professional/StatementsGuidelines/ByPublicationDate/PreviousYears/Classification-of-Functional-Capacity-and-Objective-Assessment_UCM_423811_Article.jsp. Accessed 14 Apr 2015.
- Campeau L. The Canadian Cardiovascular Society grading of angina pectoris revisited 30 years later. Can J Cardiol. 2002;18(4):371–9.PubMedGoogle Scholar
- Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation. 1978;58(6):1072–83.View ArticlePubMedGoogle Scholar
- Kampmann C, Wiethoff CM, Wenzel A, Stolz G, Betancor M, Wippermann CF, et al. Normal values of M mode echocardiographic measurements of more than 2000 healthy infants and children in central Europe. Heart. 2000;83(6):667–72.View ArticlePubMedPubMed CentralGoogle Scholar
- Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification. Eur J Echocardiogr. 2006;7(2):79–108.View ArticlePubMedGoogle Scholar
- Devereux RB, Koren MJ, de Simone G, Roman MJ, Laragh JH. Left ventricular mass as a measure of preclinical hypertensive disease. Am J Hypertens. 1992;5(6 Pt 2):S175–81.Google Scholar
- Dumesnil JG, Shoucri RM, Laurenceau JL, Turcot J. A mathematical model of the dynamic geometry of the intact left ventricle and its application to clinical data. Circulation. 1979;59(5):1024–34.View ArticlePubMedGoogle Scholar
- National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2 Suppl 1):S1–266.Google Scholar
- MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet. 2001;38(11):769–75.View ArticlePubMedPubMed CentralGoogle Scholar
- MacDermot KD, Holmes A, Miners AH. Natural history of Fabry disease in affected males and obligate carrier females. J Inherit Metab Dis. 2001;24 Suppl 2:13–4. discussion 1–2.View ArticlePubMedGoogle Scholar
- MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet. 2001;38(11):750–60.View ArticlePubMedPubMed CentralGoogle Scholar
- Kampmann C, Wiethoff CM, Whybra C, Baehner FA, Mengel E, Beck M. Cardiac manifestations of Anderson-Fabry disease in children and adolescents. Acta Paediatr. 2008;97(4):463–9.View ArticlePubMedGoogle Scholar
- Uchino M, Uyama E, Kawano H, Hokamaki J, Kugiyama K, Murakami Y, et al. A histochemical and electron microscopic study of skeletal and cardiac muscle from a Fabry disease patient and carrier. Acta Neuropathol. 1995;90(3):334–8.View ArticlePubMedGoogle Scholar
- Mehta A, West ML, Pintos-Morell G, Reisin R, Nicholls K, Figuera LE, et al. Therapeutic goals in the treatment of Fabry disease. Genet Med. 2010;12(11):713–20.View ArticlePubMedGoogle Scholar