Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new variant form of Fabry disease with hypertrophic cardiomyopathy of late onset is reported. Two unrelated male hemizygotes of this disease first presented with signs and symptoms of cardiomyopathy after 50 years of age. Cultured lymphoblastoid cells showed significantly higher residual alpha-galactosidase A activities than in the patients with classical phenotypic expressions.
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PMID:Hypertrophic cardiomyopathy in late-onset variant of Fabry disease with high residual activity of alpha-galactosidase A. 164 38

Fabry's disease was diagnosed in an adult patient as a lipid storage-induced non-obstructive hypertrophic cardiomyopathy. Stable angina pectoris started 15 years before death, was followed by slowly progressive heart failure and repeated pulmonary thromboembolism with death at 63 years. Autopsy disclosed enormous cardiomegaly (1100 g), cardiac storage of ceramide trihexoside (CTH) of the same intensity as in classical cases of generalized Fabry's disease (11 mg lipid/g wet weight) restricted to cardiocytes. Other tissues (liver, kidney, brain, pancreas, pulmonary artery, coronary arteries) were free of storage. Using proton magnetic resonance analysis on formaldehyde-fixed tissue the stored CTH was identified as globotriaosylceramide. It was enzymatically degradable by control cell cultures but left uncleaved by mutant reference Fabry cells. Alpha-galactosidase activities in peripheral leucocytes of all four of the patient's daughters were in the heterozygous range. The diagnostic difficulties in this monosymptomatic novel variant of Fabry's disease are stressed.
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PMID:Cardiocyte storage and hypertrophy as a sole manifestation of Fabry's disease. Report on a case simulating hypertrophic non-obstructive cardiomyopathy. 217 54

Four patients with Fabry's disease diagnosed by right ventricular endomyocardial biopsy had cardiac manifestations simulating hypertrophic cardiomyopathy (HCM). Case 1: A 51-year-old woman, whose elder sister had congestive heart failure, was hospitalized for exertional dyspnea and cardiomegaly. Her electrocardiogram (ECG) showed a short PQ interval (0.10 sec) and left ventricular hypertrophy. Her echocardiogram (Echo) showed moderate symmetrical hypertrophy of the left ventricle (IVST/PWT = 18 mm/17 mm). Case 2: A 32-year-old woman, whose elder sister had an abnormal ECG, was hospitalized for the ECG abnormalities consisting of a short PQ interval (0.10 sec) and ST-T changes in the left precordial leads. The Echo revealed mild symmetrical hypertrophy of the left ventricle (IVST = 13 mm, PWT = 13 mm). Case 3: A 44-year-old man was hospitalized for his ECG suggestive of left ventricular hypertrophy, and his Echo showed asymmetrical septal hypertrophy (ASH; IVST = 22 mm). Case 4: A 51-year-old man was hospitalized for his ECG showing high voltage in the left precordial leads, and his Echo showed ASH (IVST = 20 mm). The cardiac histopathological findings of these cases included cytoplasmic vacuolization by light microscopy, and electron-dense deposits consisting of parallel or concentric lamellae with periodic spacing, suggesting Fabry's disease. The urinary glycolipids of Case 1 were increased biochemically; then the diagnosis of Fabry's disease was confirmed. Cardiac hypertrophy in Fabry's disease has many aspects, because the histopathological changes and clinical manifestations are determined by genetic factors. It was concluded that Fabry's disease may be concealed in some patients with the clinical diagnosis of HCM.
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PMID:[Four cases of Fabry's disease mimicking hypertrophic cardiomyopathy]. 297 98

Light-, electron microscopic and enzyme histochemical examinations (phosphorylase, LDH, NADH:TR, SDH and 3-HBDH) were performed on endomyocardial biopsies of 26 patients with heart diseases of unknown etiology. On the basis of the clinical findings the patients were grouped into hypertrophic cardiomyopathy patients), dilated-congestive cardiomyopathy (8 patients), latent cardiomyopathy and small vessel disease (11 patients) and myocarditis (4 patients). Morphologic changes which might characterize the pathogenesis, were found in 7 patients: small vessel disease in 3 patients, nonspecific myocarditis in 1, iron storage disease in 1, adriamycin cardiomyopathy in 1 and cardiomyopathy with inclusions typical of Fabry's disease in 1 patient. In the other patients the morphologic changes were not sufficiently characteristic to be indicative of an etiopathogenesis. Several pathologic alterations did, nonetheless, appear to have a certain prognostic value such as endocardial and interstitial fibrosis, myofibrillolysis, myolysis, mitochondrial degeneration and increased lipid content in the muscle fibers. The frequency of these changes was evaluated partly semiquantitatively, partly by means of the point-counting method and graded with 1-3 points. Three patients with congestive cardiomyopathy scored at least 7 points. Two of them died within 8 weeks, 1 patient with adriamycin cardiomyopathy recovered after discontinuation of the therapy but he died 4 years after the biopsy. Six to 50 months after the biopsy (mean 31.5, median 6.5) the score was less than 7 in the other patients and all these patients were still alive. The histochemical changes manifested as an increase and/or a decrease of the enzymatic activities, involving scattered muscle fibers or their segments. A decrease of the activities of all dehydrogenases examined appeared to be prognostically ominous, correlating with a score of 7 or higher. A decrease of SDH activity in 7 cases, in combination with a decrease of the HBDH activity in 4 of them, was indicative of a disturbance in the Krebs cycle and lipid metabolism in the absence of ischemic damage. The alterations in the phosphorylase activity did not, however, appear to have a prognostic significance. Normal activity of the phosphorylase seemed to be prognostically favorable.
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PMID:The usefulness of an endomyocardial biopsy in heart disease of unknown etiology. 301 87

A 55 year old woman with heterozygous Fabry's disease presented with cardiac symptoms. The electrocardiogram showed a PR interval of 0.12 s and giant negative T waves, suggesting apical hypertrophic cardiomyopathy. Endomyocardial biopsy, however, revealed myelin like substances characteristic of Fabry's disease. Increasing thickness of the left ventricular wall was seen by echocardiography over a period of five years. A deficiency of alpha galactosidase activity in the leucocytes confirmed the diagnosis of Fabry's disease, although this patient had neither angiokeratoma or proteinuria. The possibility of Fabry's disease should be considered in patients with cardiomegaly of unknown cause and the following electrocardiographic abnormalities: a PR interval less than or equal to 0.12 s, high voltage QRS complexes in the left precordial leads, and giant negative T waves.
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PMID:A case of heterozygous Fabry's disease with a short PR interval and giant negative T waves. 310 63

New clinicopathological phenotypes are described in this report. A subclinical form of cholesterol ester storage disease was diagnosed in two adult female patients with hyperlipoproteinaemia type IIb. Both were profoundly deficient in acid lipase activity. Fabry's disease was described with intensive storage of globotriaosyl ceramide restricted solely to the heart muscle which was enormously hypertrophic. The clinical course resembled that of idiopathic hypertrophic cardiomyopathy. The variants of sphingomyelinase deficiency type A described previously are reviewed and their clinical course revised. Two of the three patients with the minimal neurological lesion still display, after a four year interval, a stable course (ages 7 and 14 years) while the neurological status of the third one (aged 8 years) deteriorated profoundly. The clinical condition of the two cases with protracted neurovisceral symptomatology (aged now 29 and half, and 30 years) is unchanged.
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PMID:New findings in pathology of storage. 838 10

Histochemical and electron microscopic studies were performed in an attempt to clarify the muscle pathology in an 18-year-old man with Fabry disease, showing proximal limb muscle atrophy, and his 52-year-old mother, who is a Fabry carrier with hypertrophic cardiomyopathy. Despite the relatively mild myopathic changes revealed by histochemistry, electron microscopy demonstrated the widespread accumulation of abundant lamellated bodies in myofibers, associated with increased glycogen granules and autophagic vacuoles. The cardiac muscle of the proband's mother revealed a mosaic pattern of normal-appearing and hypertrophic myofibers containing a number of ring-like, lamellated bodies. Although further studies are necessary to support our findings, skeletal muscle is apparently involved in patients with Fabry disease, and a mosaic pattern of cardiac muscle involvement possibly reflecting Lyonization, may be one of the characteristic findings of a Fabry disease carrier.
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PMID:A histochemical and electron microscopic study of skeletal and cardiac muscle from a Fabry disease patient and carrier. 852 10

A case of cardiac variant of Fabry's disease mimicking hypertrophic cardiomyopathy is reported. The diagnosis was obtained by biventricular endomyocardial biopsy showing severely hypertrophied myocardiocytes with large periodic acid-Schiff and Sudan black positive perinuclear vacuoles, shown at electromicroscopy to consist of lamellated cytoplasmic figures highly suggestive of Fabry's disease, and confirmed by diagnostic low activity of alpha-galactosidase A in the peripheral lymphocytes. Invasive approach was suggested by the occurrence of a long-standing atrial fibrillation that failed to determine deterioration of cardiac function. Differential diagnosis between hypertrophic cardiomyopathy and the cardiac variant of Fabry's disease is relevant for prognostic and therapeutic implications including the perspective of an enzyme replacement therapy.
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PMID:Cardiac variant of Fabry's disease mimicking hypertrophic cardiomyopathy. 1038 54

Fabry's disease is one of the lysosomal disorders. It is due to a hereditary alpha-galactosidase A defect with X-linked recessive transmission. A majority of hemizygotes develop severe multisystemic involvement (classic form), dominated by relentless renal failure and progressive neurological and cardiac lesions. Nevertheless, some affected individuals retain sufficient enzyme activity and long remain asymptomatic (atypical form); their main manifestation is hypertrophic cardiomyopathy. Female carriers are usually asymptomatic; 15%, however, have severe involvement of one or more organs. Laboratory, histological and molecular diagnosis identifies 100% of hemizygotes and over 80% of heterozygotes. With recent developments in molecular genetics it is possible to produce the human recombinant enzyme alpha-GALA. Its effects in hemizygous patients remain to be evaluated. In addition, the results of a trial of gene therapy in a Fabry's disease gene knocked-out mouse appear promising. These new therapeutic approaches will probably soon provide substitutive treatment for Fabry's disease as well as for so-called "orphan" diseases.
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PMID:[Fabry disease: clinical aspects and therapeutic perspectives]. 1090 84

The variant form of Fabry's disease, called cardiac Fabry's disease, which has left ventricular hypertrophy as its main clinical manifestation is not uncommon. Because there has been no pedigree analysis in families with cardiac Fabry's disease, we performed gene analyses, enzyme assays, and cardiac evaluations in 3 distinct families with cardiac Fabry's disease. Gene analyses were performed in all 18 members of 3 families including 3 male probands. Five hemizygotes and 6 heterozygotes were identified. Plasma alpha-galactosidase A activity was measured in all 18 family members. Echocardiography and electrocardiography were performed in the 5 hemizygotes and in 5 of the 6 heterozygotes. The proband and 3 heterozygotes from a pedigree with a mutation in exon 6 of the alpha-galactosidase A sequence leading to a Met296Ile substitution showed a decrease in alpha-galactosidase A activity. In a separate pedigree, a proband and his hemizygous brother, with a mutation in exon 2 leading to a Glu66Gln substitution, had a decrease in alpha-galactosidase A activity, whereas 3 heterozygotes had normal values. In the third pedigree, a decrease in alpha-galactosidase A activity was observed in 2 hemizygotes who have a mutation in exon 1 leading to an Ala2OPro substitution. Although all 5 hemizygotes exhibited left ventricular hypertrophy on echocardiography, all 5 heterozygotes lacked this finding. Because plasma alpha-galactosidase A activity was normal in some heterozygotes with cardiac Fabry's disease, gene analysis is essential for an accurate diagnosis. Patients with cardiac Fabry's disease thus show an x-linked form of hypertrophic cardiomyopathy.
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PMID:Molecular genetic, biochemical, and clinical studies in three families with cardiac Fabry's disease. 1113 37


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