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Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many metabolic diseases result in pathological changes within the cardiovascular system, often with the most severe effects on the function of the heart and great vessels. Metabolic disorders affecting the heart include disorders of amino acid metabolism, storage diseases, neuromuscular diseases, diseases of metal and pigment metabolism, carnitine deficiency, and connective tissue disorders. Several inborn errors of metabolism may involve the myocardium due to the accumulation of abnormal metabolites in the myocardial cells. In addition, the heart valves and coronary vessels may be involved. If the predominant effect is in the myocardial cell, it will be manifested clinically as a cardiomyopathy. Some disorders, in particular oxalosis, may involve the conduction system as a result of the deposition of oxalate crystals and result in conduction disturbances such as in alkaptonuria, primary oxalosis, and homocystinuria. Myocardial involvement may result in cardiomyopathy of the three functional types: (1) congestive, as in Fabry's disease, (2) hypertrophic, as in glycogen storage disease, type II, or (3) restrictive, as in Gaucher's disease. In the storage disease severe valvular as well as myocardial involvement occur predominantly in the glycogen storage diseases, types II-IV, mucolipidoses, sphingolipidoses, and neuronal ceroid lipofuscinosis. There are a variety of neuromuscular disorders that may be associated with cardiomyopathy, including the muscular dystrophies, Friedreich's ataxia, and Kugelberg-Welander syndrome. The pathological features of these conditions are not specific, but result usually in a congestive form of cardiomyopathy. Patients with metal and pigment metabolic disorders include iron storage disease, either hemochromatosis or transfusional hemosiderosis, Menkes' kinky hair syndrome, and Dubin-Johnson syndrome. Either a restrictive or a congestive form of cardiomyopathy may occur. The systemic form of carnitine deficiency is an autosomal recessive disorder and may present as a cardiomyopathy with congestive heart failure and lipid accumulation in the myocardial cells. Connective tissue disorders are generalized diseases that may involve the heart and valvular tissue, but also the blood vessels. These include Marfan's syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta, and pseudo-xanthoma elasticum.
Am J Cardiovasc Pathol 1987
PMID:The effects of metabolic diseases on the cardiovascular system. 333 40

Enzyme replacement therapy has recently been introduced to treat Fabry disease, a rare X-linked lysosomal storage disorder. The disease occurs due to deficient activity of alpha-galactosidase A, leading to progressive accumulation of globotriaosylceramide in multiple organs and tissues. Renal, cardiac and cerebrovascular manifestations of the disease result in premature death in both hemizygous males and heterozygous females. This paper outlines the clinical signs, symptoms and diagnosis of Fabry disease, and the development of the two available enzyme replacement therapies -- agalsidase alfa and agalsidase beta. Agalsidase alfa and agalsidase beta are produced in a human cell line and in Chinese hamster ovary cells, respectively, resulting in products with the same amino acid sequence as the native human enzyme, but with different patterns of glycosylation. Correct post-translational glycosylation is important in terms of the pharmacokinetics, biodistribution, clinical efficacy and tolerability of genetically engineered protein therapeutics. Differences in glycosylation, which may affect immunogenicity and mannose-6-phosphate receptor-mediated cellular internalisation of administered enzyme, possibly account for the differences in dosing, clinical effects and safety profiles reported for agalsidase alfa and agalsidase beta.
Curr Med Chem Cardiovasc Hematol Agents 2004 Oct
PMID:Efficacy of enzyme replacement therapy in Fabry disease. 1532 Jul 78

Coronary flow reserve was assessed in a patient with Anderson-Fabry disease complicated by symmetric left ventricular hypertrophy. Coronary flow reserve was measurable in all three major coronary arteries providing an opportunity to compare regional coronary flow reserve from different vascular beds. In this patient all the three vascular beds supplied diffusely hypertrophied myocardium. Coronary flow disturbances in small intramyocardial perforating arteries were visible. The coronary flow reserve was reduced to a similar level (around to 2.0) in all three major arteries. In our patient with Anderson-Fabry disease, the coronary vasodilatation was blunted in a diffuse pattern corresponding to the myocardial hypertrophy distribution. In small intramyocardial arteries coronary flow was also disturbed. Accordingly, retrograde systolic flow and accelerated anterograde diastolic flow were documented.
Cardiovasc Ultrasound 2005 Apr 27
PMID:Reduced coronary flow reserve in Anderson-Fabry disease measured by transthoracic Doppler echocardiography. 1585 18

This case illustrates the utility of CMR in evaluating a patient with undiagnosed Anderson-Fabry disease who presented with chest pain, elevated cardiac biomarkers, normal coronary arteries, and an abnormal echocardiogram.
J Cardiovasc Magn Reson 2006
PMID:Detection of Anderson-Fabry cardiomyopathy with CMR in a patient with chest pain and elevated cardiac biomarkers. 1666 84

Anderson-Fabry Disease (AFD) is a storage disease that mimics hypertrophic cardiomyopathy. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance occurs in approximately 50% of patients in the basal inferolateral LV wall, but how an intracellular storage disease causes focal LGE is unknown. We present a whole-heart histological validation that LGE is caused by focal myocardial collagen scarring. This scarring may be the substrate for electrical re-entry and sudden arrhythmic death. The reasons for this distribution of fibrosis are unclear, but may reflect inhomogeneous left ventricular wall stress.
J Cardiovasc Magn Reson 2006
PMID:The histological basis of late gadolinium enhancement cardiovascular magnetic resonance in a patient with Anderson-Fabry disease. 1675 35

Fabry disease is an inherited enzyme deficiency of galactosidase A that results in various phenotypes: classic, cardiac or renal. It can present variably and may represent an important cause of occult neurological and cardiac syndromes and renal failure. Preclinical and clinical studies demonstrate effectiveness of enzyme infusion in controlling and preventing these manifestations of the disease.
Timely Top Med Cardiovasc Dis 2006 Apr 01
PMID:Fabry disease. 1651 11

Fabry disease is caused by a deficiency of a-galactosidase A which leads to the progressive intra-lysosomal accumulation of ceramide trihexoside (CTH), also known as globotriaosylceramide (Gb3), in different cell types and body fluids. The clinical manifestations are multisystemic and predominantly affect the heart, kidney and central nervous system. The role of CTH in the pathophysiological process of Fabry disease is not established, and the link between the degree of accumulation and disease manifestations is not systematic. The use of CTH as a diagnostic tool has been proposed for several decades. The recent introduction of a specific treatment for Fabry disease in the form of enzyme replacement therapy (ERT) has led to the need for a biological marker, in place of a clinical sign, for evaluating the efficacy of treatment and also as a tool for following the long term effects of treatment. The ideal biomarker must adhere to strict criteria, and there should be a correlation between the degree of clinical efficacy of treatment and a change in its concentration. This review of the literature assesses the utility of CTH as a diagnostic tool and as a marker of the efficacy of ERT in patients with Fabry disease. Several techniques have been developed for measuring CTH; the principles and the sensitivity thresholds of these methods and the units used to express the results should be taken into consideration when interpreting data. The use of CTH measurement in Fabry disease should be re-evaluated in light of recent published data.
Cardiovasc Hematol Agents Med Chem 2006 Oct
PMID:The role of ceramide trihexoside (globotriaosylceramide) in the diagnosis and follow-up of the efficacy of treatment of Fabry disease: a review of the literature. 1707 6

Deficiency of alpha-galactosidase A (GLA) (Fabry disease) leads to the accumulation of glycosphingolipids in the vasculature leading to multiorgan pathology. In addition to well-described microvascular disease, deficiency of GLA is also characterized by premature macrovascular events such as stroke and possibly myocardial infarction. The mechanisms by which GLA may influence macrovascular disease are unclear. A mouse model of GLA deficiency has facilitated the study of glycosphingolipid metabolism abnormalities on macrovascular end points. This review addresses some of the potential pathways by which GLA deficiency may contribute to vascular complications.
Trends Cardiovasc Med 2007 May
PMID:Alpha-galactosidase A in vascular disease. 1748 95

Progressive left ventricular hypertrophy is the hallmark of cardiac manifestations in patients with Fabry disease. Cardiovascular magnetic resonance with tissue tagging allows detailed assessment of the cardiac motion pattern. The aim was to test the hypothesis that not only Fabry patients with severe left ventricular hypertrophy exhibit changes in myocardial motion, but also Fabry patients with normal left ventricular mass. Magnetic resonance tagging using slice following complementary spatial modulation of magnetization (CSPAMM) combined with harmonic phase analysis (HARP) was applied to measure left ventricular shortening and contraction. Additionally, left ventricular rotation and global left ventricular torsion were examined. Twenty-nine Fabry patients grouped in patients with (n = 13) and without (n = 16) left ventricular hypertrophy were compared with 29 age and sex matched healthy volunteers. Long axis shortening and circumferential contraction showed reduced peak values with increasing left ventricular mass and were significantly reduced in Fabry patients with left ventricular hypertrophy (p < 0.001 and p < 0.05, respectively). Torsional deformation and apical rotation were increased both in Fabry patients with left ventricular hypertrophy as well as in patients with normal left ventricular mass (p < 0.001 for torsion) compared with controls. Applying the magnetic resonance tagging acquisition and analysis methods, myocardial motion abnormalities could not only be measured in Fabry patients with left ventricular hypertrophy but also in patients without macroscopic cardiac involvement.
J Cardiovasc Magn Reson 2007
PMID:Altered myocardial motion pattern in Fabry patients assessed with CMR-tagging. 1806 49

Late gadolinium enhancement cardiovascular magnetic resonance (CMR) can visualize myocardial interstitial abnormalities. The aim of this study was to assess whether regions of abnormal myocardium can also be visualized by late enhancement gadolinium CMR in the specific cardiomyopathies. A retrospective review of all referrals for gadolinium CMR with specific cardiomyopathy over 20 months. Nine patients with different specific cardiomyopathies were identified. Late enhancement was demonstrated in all patients, with a mean signal intensity of 390 +/- 220% compared with normal regions. The distribution pattern of late enhancement was unlike the subendocardial late enhancement related to coronary territories found in myocardial infarction. The affected areas included papillary muscles (sarcoid), the mid-myocardium (Anderson-Fabry disease, glycogen storage disease, myocarditis, Becker muscular dystrophy) and the global sub-endocardium (systemic sclerosis, Loeffler's endocarditis, amyloid, Churg-Strauss). Focal myocardial late gadolinium enhancement is found in the specific cardiomyopathies, and the pattern is distinct from that seen in infarction. Further systematic studies are warranted to assess whether the pattern and extent of late enhancement may aid diagnosis and prognostic assessment.
J Cardiovasc Med (Hagerstown) 2007 Dec
PMID:Myocardial late gadolinium enhancement in specific cardiomyopathies by cardiovascular magnetic resonance: a preliminary experience. 1816 27


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