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)

Angiokeratoma corporis diffusum (Fabry's disease) is an X-linked disorder of glycosphingolipid catabolism. Heterozygous females, although usually asymptomatic, are occasionally as severely afflicted as hemizygous males; recently we identified a heterozygous patient with cardiomyopathy and severe pain in the extremities. In order to elucidate the difference of the clinical features, we analyzed the glycolipid composition of the heart, liver, and kidney obtained from the patient and from a hemizygote. Gas-liquid chromatography revealed that globotriaosylceramide (Gb3) was markedly increased in the heart (32.4 times higher than control) and increased to a lesser extent in the liver and kidney (3.74 and 6.79 times, respectively). The pattern of Gb3 accumulation in the heterozygote, where the highest increases were seen in the heart, was distinct from that in the hemizygote, where elevated levels of Gb3 and Ga2 were found in the kidney. Furthermore, the alpha-galactosidase activity in the heart, liver, and kidney of the heterozygote was 17%, 26%, and 36%, respectively, of normal controls, which correlated well with the accumulation of glycosphingolipid in the heart and with the disease's clinical manifestations. Two other hemizygotic patients, who were identified by low alpha-galactosidase activities, demonstrated the cardiac involvement.
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PMID:Biochemical and clinical analysis of accumulated glycolipids in symptomatic heterozygotes of angiokeratoma corporis diffusum (Fabry's disease) in comparison with hemizygotes. 215 88

Seven patients with Fabry's disease and severe pain received carbamazepine (CMZ). Five of 7 patients had moderate to complete relief based upon self-assessment of pain levels. Preexisting autonomic dysfunction was exacerbated by CMZ in 2. Complications encountered were ileus, urinary retention, and gastrointestinal disturbance. Although CMZ was useful in treatment of pain, caution should be employed in this disease.
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PMID:Carbamazepine in Fabry's disease: effective analgesia with dose-dependent exacerbation of autonomic dysfunction. 249 69

Fabry's disease is an X-linked disorder of glycolipid catabolism. We have found a symptomatic heterozygous female with cardiomyopathy and severe pain in the extremities. We studied histochemically and biochemically the accumulated glycolipids in spinal and sympathetic ganglia of the patient. Histochemical examination demonstrated the marked glycolipid deposits that have been observed in heterozygous males in these ganglia. Gas-liquid chromatography (GLC) revealed that these accumulated glycolipids were characterized as globotriaosylceramide (Gb3cer) and galabiosylceramide (Ga2cer). In the heterozygous female, the accumulations of Gb3cer in spinal and sympathetic ganglia were, respectively, 34 and 48 times the amount in normal controls. This is the first report on quantitative and qualitative analyses of the accumulated glycolipids in spinal and sympathetic ganglia of a heterozygous carrier female.
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PMID:Accumulation of glycosphingolipids in spinal and sympathetic ganglia of a symptomatic heterozygote of Fabry's disease. 250 Apr 99

Fabry-Anderson's disease or angiokeratoma corporis diffusum (ACD) is an X-linked sphingolipidosis with a systemic character and occurs in 2-5 per million births (1-3). The basic defect is the absence of a lysosomal enzyme x-galactosidase A. This enzyme is necessary for the metabolization of ceramide trihexoside (globotriglycosyl ceramide), a breakdown product of cell membranes (4, 5). Clinically the disease is characterized by cutaneous angiokeratoma's and severe pain in the limbs from the second decade, followed by progressive renal insufficiency and cardiovascular and cerebrovascular damage in the third or fourth decade (6-8). In patients with established ACD, gastrointestinal symptoms have been described incidentally, mainly mild diarrhea (9, 10). We describe a kindred with ACD showing two extraordinary clinical features: (1) Anorexia, weight loss, and diarrhea were the presenting symptoms and antedated limb pain by many years, which has not been described before. (2) The disease was associated with another rare X-linked disorder: hypoplastic amelogenesis imperfecta.
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PMID:Anorexia, weight loss, and diarrhea as presenting symptoms of angiokeratoma corporis diffusum (Fabry-Anderson's disease). 251 Sep 82

Originally described as a dermatologic curiosity by Fabry in 1898 and independently by Anderson in the same year, Fabry disease is now recognized as an inborn error of glycosphingolipid metabolism resulting from the defective activity of the lysosomal enzyme, alpha-galactosidase A (see Desnick and Sweeley for a comprehensive review). The enzymatic defect, transmitted by an X-linked recessive gene, leads to the accumulation of neutral glycosphingolipids with terminal alpha-galactosyl residues in the plasma and in the lysosomes of endothelial, perithelial, and smooth muscle cells of the cardiovascular-renal system and, to a lesser extent, in reticuloendothelial, myocardial, and connective tissue cells. Epithelial cells in the kidney, cornea, and other tissues contain the lysosomal depositions, as do the ganglia and perineural cells of the autonomic nervous system. The major accumulated substrate is globotriaosylceramide [galactosyl-(alpha 1----4)-galactosyl-(beta 1----4)-glucosyl-(beta 1----1')-ceramide]; another substrate, galabiosylceramide [galactosyl-(alpha 1----4)-galactosyl-(beta 1----1')-ceramide] is deposited primarily in renal lysosomes. The clinical manifestations of Fabry disease are the sequelae of the anatomical and physiologic alterations produced by progressive glycosphingolipid deposition. Clinical onset of the disease in hemizygous males usually occurs during childhood or adolescence, with periodic crises of severe pain in the extremities (acroparesthesias), the appearance of the vascular cutaneous lesions (angiokeratoma), hypohidrosis, and the characteristic corneal dystrophy. With increasing age, the major morbid symptoms of the disease result from the progressive infiltration of glycosphingolipid in the cardiovascular-renal system. Death usually occurs from renal, cardiac, or cerebral complications of the vascular disease. Prior to the availability of treatment by renal transplantation or dialysis, the average age at death for affected males was about 40 years. Heterozygous females, who may exhibit the disease in an attenuated form, are most likely to have only corneal opacities. Previously, the diagnosis of affected hemizygous males and heterozygous females was based on clinical findings and the levels of alpha-galactosidase A activity in easily obtained sources, e.g., plasma and isolated lymphocytes or granulocytes. Because the gene encoding alpha-galactosidase A undergoes random X-inactivation, the expressed level of enzymatic activity in females heterozygous for the disease gene may vary significantly, thereby making accurate carrier detection difficult.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Fabry disease: molecular genetics of the inherited nephropathy. 256 47

A report is presented on biochemical studies of the fibroblasts from a 26-year-old man with Fabry's disease whose clinical picture was atypical. The patient had severe pain in the extremities, but no angiokeratomas, corneal clouding or hypohidrosis. The trihexosylceramidase activity in the fibroblasts in vitro was deficient. The level and Km value of the residual activity were similar to levels seen in typical Fabry's patients. However, fibroblasts from the patient cultured in medium supplemented with [3H]ceramide trihexoside hydrolyzed the labeled ceramide trihexoside much higher than did cells from typical Fabry's patients, implying that the patient has a partial defect in hydrolysis of trihexosylceramide in cultured fibroblasts.
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PMID:Fabry's disease with partially deficient hydrolysis of ceramide trihexoside. 298 38

A 28-year-old Korean man suffered from generalized acquired anhidrosis and heat intolerance that were confirmed by a sweat test. Other clinical features consistent with Fabry's disease were fever and severe pain of the lower extremities and leg edema. Although the patients lacked cutaneous angiokeratomas, ultrastructural studies of the normal skin demonstrated diagnostic intracytoplasmic inclusions in the endothelial cells and pericytes of dermal vessels, fibroblasts, perineural cells, and secretory cells of eccrine glands. alpha-Galactosidase assay of the patient's leukocytes showed markedly decreased activity, which confirms the diagnosis.
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PMID:Generalized anhidrosis associated with Fabry's disease. 311 82

A clinical review and histopathological study of three cases of Anderson-Fabry disease is presented and pathological changes in the central and peripheral nervous systems are reported, in some sites for the first time. These are telangiectatic changes in vessels of the sympathetic ganglia in the vertebral trunk; storage of glycolipid in pigmented cells of the substantia nigra and in anterior horn cells; and degeneration of nerve fibres in the dorsal root entry zone and substantia gelatinosa of the spinal cord. The histopathological findings suggest that in this disease pain is due to involvement of dorsal root ganglion cells with associated axonal degeneration of the small fibres in pathways subserving pain.
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PMID:Anderson-Fabry disease: a histopathological study of three cases with observations on the mechanism of production of pain. 420 59

A man with Fabry's disease, who died at 52, suffered from lancinating limb pains between the age of 20 and 27, and from severe arthralgia between 20 and 40. The sural nerve showed a severe loss of fibers (1,614 myelinated fibers/mm2), chiefly affecting the small myelinated fibers. Inclusions of both homogeneous and lamellated appearance were present in the perineurial cells, fibroblasts and vessel walls. Teased fibers displayed moderate remyelination, regeneration and the presence of globular focal myelin thickening. The transient time course of painful manifestations in this case is stressed in view of a possible pathogenesis of pain in Fabry's disease. It appears that small-fiber neuropathy is not directly related to the occurrence of pain symptoms, since the prevalent loss of small myelinated fibers was seen in the absence of actual pain. The small sensory neurons in the dorsal root ganglia, that are especially affected by lipid accumulation, probably give rise to abnormal discharges producing pain via the prevalence of the small-fiber versus the large-fiber input to the dorsal horn of the spinal cord (gate control theory). Thus pain fits may spontaneously abate, as in our case, if degeneration and loss of the small sensory neurons overstep a critical level.
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PMID:Pathological study of the sural nerve in Fabry's disease. 608 46

The present case is a 24-years-old man who complained painful attack with numbness in both bilateral shoulder regions and distal extremities. This pain was increased by the stimulations of sunlight and heat. On physical examinations, he had an acromegalic-like-appearance, thick mustache and beard. Malocclusion of the teeth which showed the broad space was found. And skin lesion was not found out. Hypesthesia in bilateral distal extremities was revealed and no other abnormal neurological findings were observed. He was made diagnosis of Fabry's disease by laboratory examinations which were alpha-galactosidase deficiency analysed in leukocytes, increased ceramide trihexosides demonstrated in urinary sediment and electron microscopic findings in the biopsy of the skin and sural nerve. His mother had and decreased alpha-galactosidase activity which levels showed between normal and patient and was speculated to be a carrier. On an electron microscopy, "Zebra body" was observed in fibroblasts, capillary endothelial cells, their pericytes, prineural and Schwann cells. Many of them had a distinct limiting membrane and laminal structure with irregular alterations of light and dark zone. In the cytoplasma of Schwann cells, there were many rough endoplasmic reticulums which were located parallel with alignment and seemed to show the loosed laminal structure with the unclear limited membrane. Occasionally, fusions between irregular laminal structure and rough endoplasmic reticulum were also observed. These findings could be indicated that the formation of Zebra body is related to rough endoplasmic reticulum, because laminal structure which described above is corresponded to pre-Zebra body. In the cytoplasma of the prineural cells, recket-like structure which was seen in histiocytosis X were occasionally observed.
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PMID:[Fabry's disease with malocclusion and acromegalic-appearance: clinical and electromicroscopic studies (author's transl)]. 624 68


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