RESUMEN
A Fabry heterozygote with early clinical manifestations of this X linked disorder is described. Her symptoms, including febrile attacks, arthralgia, abdominal pain, and neurological signs, were characteristic of Fabry's disease hemizygotes. The neurological findings were compatible with a brain stem infarction. The diagnosis was confirmed by the finding of low activities of alpha-galactosidase A (alpha-galA) in plasma, lymphocytes, and cultured fibroblasts, and by the observation of typical lamellar inclusions in the lysosomes of cultured fibroblasts. Increased levels of ceramide trihexoside were also found by TLC of urine sediment. The family history gave no indication of Fabry's disease in the patient's relatives, and biochemical and ultrastructural investigations of their cells were also normal. Our findings therefore suggest that the defective gene in the heterozygote has resulted from a new mutation.
Asunto(s)
Enfermedad de Fabry/genética , Heterocigoto , Mutación , Adolescente , Células Cultivadas , Enfermedad de Fabry/metabolismo , Enfermedad de Fabry/ultraestructura , Femenino , Fibroblastos/enzimología , Fibroblastos/ultraestructura , Frecuencia Cardíaca , Humanos , Linfocitos/enzimología , alfa-Galactosidasa/sangre , alfa-Galactosidasa/metabolismoRESUMEN
A family with Fabry's disease including 2 hemizygotes and 3 heterozygotes is reported. The ocular manifestations include tortuosity of conjunctival vessels, Fabry's deposits underlying the anterior capsule of the lens and the whorl-like corneal dystrophy. Foam cells or mulberry cells in the urinary sediment and varying numbers of high electron-dense inclusions in the cytoplasm of endothelial cells in skin lesions are also important in diagnosing this disease. The concentrations of lipid peroxide in the sera of 2 hemizygotes in this report were higher than normal, possibly due to the patients weak ability of anti-oxygenation and malfunction of cells whose plasma membranes are easily attacked by free oxygen radicals. The biochemical and pathological changes, diagnosis, treatment, genetics and prevention of the disease are discussed.
Asunto(s)
Enfermedad de Fabry/genética , Piel/ultraestructura , Adulto , Biopsia , Conjuntiva/irrigación sanguínea , Ojo/patología , Enfermedad de Fabry/patología , Enfermedad de Fabry/ultraestructura , Femenino , Humanos , Cristalino/patología , Masculino , Linaje , Vasos Retinianos/patología , Piel/patología , Vénulas/patologíaRESUMEN
A 46-year-old Japanese woman had disseminated angiokeratoma, confirmed by electron microscopy which showed numerous cytoplasmic vacuoles in cells of the kidney and skin. Enzyme activities against synthetic and natural substrates in leucocytes and fibroblasts were normal. Her urine contained a large amount of sialylglycoaminoacids, with predominant excretion of an O-glycoside-linked glycoaminoacid.
Asunto(s)
Enfermedad de Fabry/orina , Glicoconjugados/orina , Enfermedad del Almacenamiento de Glucógeno/orina , Aminoácidos/orina , Biopsia , Fenómenos Químicos , Química , Enfermedad de Fabry/ultraestructura , Femenino , Enfermedad del Almacenamiento de Glucógeno/patología , Humanos , Riñón/patología , Riñón/ultraestructura , Microscopía Electrónica , Persona de Mediana Edad , Ácidos Siálicos/orina , Piel/patología , Piel/ultraestructuraRESUMEN
The skin of a patient with Fabry's diffuse angiokeratoma accompanied by a severe decrease of leucocyte alpha-galactosidase (0,7-1,2 nmol/mg protein/h) was studied by a method of semithin and ultrathin sections. Cytoplasmic inclusions having lamellar structure in the form of alternating electron-dense and light strips with a period about 6 nm were found in the endotheliocytes of dilated vessels, lymphoid cells, neutrophil leucocytes, axons and leucocytes of nerve trunks. The presence of these specific inclusions together with the decrease of leucocytic alpha-galactosidase allows the differential diagnosis with other types of angiokeratomas and some skin angiomas.
Asunto(s)
Enfermedad de Fabry/ultraestructura , Piel/ultraestructura , Adulto , Biopsia , Humanos , Cuerpos de Inclusión/ultraestructura , Masculino , Microscopía ElectrónicaRESUMEN
A 9-year-old boy, presented with disseminated angiomatous lesions on the right leg. Ultrastructural examination of muscle and peripheral nerve showed numerous lamellar inclusions characteristic of Fabry's disease in the vessel's walls and perineurial cells. In addition, there were typical lamellar inclusions in some muscle fibers. Large myelinated fibers were reduced in number and some myelinated fibers showed segmental demyelination. Some lipid deposits displaying a lamellar pattern were occasionally seen in a few myelinated and unmyelinated axons. These abnormalities of nervous fibers are uncommon in Fabry's disease.
Asunto(s)
Enfermedad de Fabry/ultraestructura , Músculos/ultraestructura , Nervios Periféricos/ultraestructura , Niño , Humanos , Pierna , Masculino , Fibras Nerviosas Mielínicas/ultraestructuraRESUMEN
In a significant number of cases, the administration of aminoglycosides induces renal failure. Electron microscopy has now shown that the renal lesion is mainly characterised by the appearance of myelin figures (myeloid bodies) in lysosomes of proximal convoluted tubules. These figures are then eliminated by urinary excretion. The search for and quantification of the myelin figures in urinary sediment seems to us to link the renal failure to the administration of aminoglycosides. Our study is based on 75 patients: 54 received aminoglycosides and 21 were controls. In each case myelin figures in the urinary sediment were grouped into one of 6 classes (O to V) according to their quantity. Comparison of the results with clinical factors showed 3 different correlations: 1) between the presence of myelin figures in the urine and the administration of aminoglycosides; 2) between the quantity of myelin figures and the accumulated dose of aminoglycosides; 3) between the quantity of myelin figures and obvious renal failure. The absence of myelin figures in control patients attests to their diagnostic value. Urine analysis to detect myelin figure appears to be a reliable technique in confirming the aminoglycoside's origin of an acute renal failure. It would also aid in determining and evaluating aminoglycoside nephrotoxicity in animal experimentation and human pathology. Since this method is non invasive, repeated studies are possible in man as well as animals.
Asunto(s)
Antibacterianos/farmacología , Túbulos Renales/ultraestructura , Riñón/efectos de los fármacos , Orina/análisis , Lesión Renal Aguda/inducido químicamente , Aminoglicósidos/farmacología , Relación Dosis-Respuesta a Droga , Enfermedad de Fabry/ultraestructura , Humanos , Lisosomas/ultraestructura , Microscopía ElectrónicaRESUMEN
Autopsy specimens of the testes and epididymis of a 32-year-old male with Fabry's disease were studied by light and electron microscopy. The characteristic ceramide deposits (lamellar inclusions, myeloid-bodies, zebra-bodies) were found in the Leydig cells as well as in the epithelial lining of both the ductuli efferentes and the ductus of the epididymis. Similar myeloid-bodies were observed in the blood vessels, connective tissue cells and muscle cells of the testicular interstitium, tunica albuginea and epididymis. In contrast, myeloid-bodies were absent or scarce in both the seminiferous epithelium and the mediastinum testis. However, the seminiferous tubules were severely affected showing reduced diameter, thickening of the tunica propria, and a few degenerated spermatogonia and primary spermatocytes. The different degrees of involvement of the testicular structures might be related to their different functions, the absorptive and permeable structures being the most severely affected. The development of testicular alterations seems to have been slow, since the patient fathered three children.
Asunto(s)
Epidídimo/patología , Enfermedad de Fabry/patología , Testículo/patología , Adulto , Epidídimo/ultraestructura , Enfermedad de Fabry/ultraestructura , Humanos , Células Intersticiales del Testículo/ultraestructura , Masculino , Microscopía Electrónica , Túbulos Seminíferos/ultraestructura , Testículo/ultraestructuraRESUMEN
Percutaneous renal biopsy was performed in a surface coal miner with radiographic and histopathologic pulmonary changes consistent with acute silicolipoproteinosis who developed proteinuria and hematuria. Electron microscopic evaluation of the renal tissue specimen revealed a diffusely thickened glomerular basement membrane, foot process effacement, and dense lamellar inclusions in swollen glomerular epithelial cells, similar to those seen in Fabry's disease. However, normal levels of plasma alpha-galactosidase A, normal urinary sediment glycosphingolipids and the absence of the clinical characteristics of Fabry's disease excluded this diagnosis. This case illustrates that electron-dense lamellar inclusions, similar to those seen in Fabry's disease, may be seen in other entities such as nephropathy associated with silicosis.
Asunto(s)
Enfermedad de Fabry/ultraestructura , Glomerulonefritis/patología , Silicosis/patología , Adulto , Diagnóstico Diferencial , Glomerulonefritis/metabolismo , Humanos , Riñón/ultraestructura , Pulmón/patología , Masculino , Silicosis/metabolismoRESUMEN
Cultured fibroblasts from a patient with Fabry's disease were treated with alpha-galactosidase A. The cells internalized the enzyme via a receptor-mediated transport system, resulting in the uptake of enzyme to 50% of the activity of normal cells. Following uptake of the enzyme and incubation for 9 days, a loss of electron-dense lamellar material within membrane-bound residual bodies was detected by electron microscopy. Morphometric analysis of electron micrographs showed that the percentage volume of cytoplasm occupied by electron-dense lamellar material in Fabry's disease fibroblasts decreased to near normal after treatment with enzyme. These results indicate that the ultrastructural abnormalities of Fabry's disease cells can be corrected by enzyme replacement, at least in cultured fibroblasts.
Asunto(s)
Enfermedad de Fabry/ultraestructura , Galactosidasas/metabolismo , alfa-Galactosidasa/metabolismo , Adulto , Células Cultivadas , Medios de Cultivo , Enfermedad de Fabry/enzimología , Fibroblastos/ultraestructura , Humanos , Masculino , Microscopía ElectrónicaRESUMEN
Fabry's disease is a rare, sex-linked disorder of glycolipid metabolism. We describe a patient with watery diarrhea, early satiety, and asymptomatic cholelithiasis. The jejunal aspirate demonstrated bacterial overgrowth; sigmoidoscopy showed rectal angiokeratoma corpora diffusum. The gastric emptying rate measured with 99mTc-sulfur colloid was markedly prolonged and the fasting gastrin was elevated at 276 pg/ml. The (14C)glycocholate breath test demonstrated a markedly elevated peak at 4 h, associated with an increased fecal bile acid loss of 0.82 g/day. Oral cholecystogram showed a solitary radiolucent stone in a functioning gallbladder. The bile acid pool size and lithogenic index were normal. Light microscopy of small bowel and rectal biopsy specimens revealed normal surface epithelium, but enlarged and vacuolated ganglion cells in Meissner's plexus. Electron microscopy showed laminated and amorphous osmiophilic deposits within ganglion cells of the submucosal plexus, within smooth muscle cells of the muscularis mucosae, and within endothelial cells lining arterioles, venules, and capillaries, but not in autonomic nerve fibers or enterocytes. The diarrhea and early satiety responded promptly to metoclopramide and to tetracycline. The early satiety was likely on the basis of delayed gastric emptying due to deposition of sphingolipid within ganglion cells of the autonomic nervous system; the diarrhea was likely on the basis of intestinal stasis with bacterial overgrowth and bile salt wastage.
Asunto(s)
Diarrea/etiología , Enfermedad de Fabry/complicaciones , Adulto , Bilis/análisis , Biopsia , Colelitiasis/etiología , Diarrea/tratamiento farmacológico , Enfermedad de Fabry/fisiopatología , Enfermedad de Fabry/ultraestructura , Vaciamiento Gástrico , Humanos , Yeyuno/microbiología , Masculino , Metoclopramida/uso terapéutico , Recto/patología , Saciedad , Tetraciclina/uso terapéuticoRESUMEN
A histochemical study was performed on light- and electron-microscopic level in a case of Fabry's disease. The patient underwent kidney transplantation for renal failure and died of heart failure 6 months later. Patient's tissues were studied at the light- and electron-microscopic levels with various embedding and staining techniques for lipids and carbohydrates. Two peroxidase-labeled lectins (from Ricinus communis and from Bandeiraea simplicifolia) known to have affinity for alpha- and beta-D-galactose, were strongly reactive with the storage material on frozen sections. The ultrahistochemical and extraction tests showed that the typical granules had a variable reactivity and morphologic characteristics in different cells, probably reflecting different composition. A small number of typical deposits were also observed in the transplanted kidney. This is the first reported case of recurrence of the storage disease in the allograft. Of interest was also the fact that the patient's blood inhibited normal alpha-galactosidase activity, suggesting a possible inhibitor-related mechanism in the pathogenesis of the recurrence.
Asunto(s)
Enfermedad de Fabry/metabolismo , Adulto , Enfermedad de Fabry/ultraestructura , Glicoesfingolípidos/metabolismo , Histocitoquímica , Humanos , Trasplante de Riñón , Masculino , Recurrencia , Trasplante HomólogoAsunto(s)
Córnea/patología , Errores Innatos del Metabolismo/patología , Errores Innatos del Metabolismo de los Aminoácidos/patología , Amiloidosis/patología , Córnea/ultraestructura , Distrofias Hereditarias de la Córnea/patología , Disautonomía Familiar/metabolismo , Disautonomía Familiar/patología , Enfermedad de Fabry/patología , Enfermedad de Fabry/ultraestructura , Enfermedad del Almacenamiento de Glucógeno/patología , Humanos , Errores Innatos del Metabolismo Lipídico/patología , Mucolipidosis/patología , Mucopolisacaridosis/patología , Tirosina/sangreAsunto(s)
Enfermedad de Fabry/ultraestructura , Fibras Nerviosas/ultraestructura , Piel/ultraestructura , Adolescente , Adulto , Biopsia , Enfermedad de Fabry/diagnóstico , Humanos , Cuerpos de Inclusión/ultraestructura , Masculino , Microcirculación/ultraestructura , Microscopía Electrónica , Persona de Mediana Edad , Piel/irrigación sanguínea , Piel/inervaciónRESUMEN
Two brothers suffering from Fabry disease, with classical dermatological and with ophthalmological symptoms, early signs of renal lesions and diminished fertility are presented. The diagnosis is verified by electronmicroscopical investigations. Good symptomic-therapeutic effect of hydantoin-derivatives was observed.
Asunto(s)
Enfermedad de Fabry/genética , Adulto , Conjuntiva/patología , Enfermedad de Fabry/metabolismo , Enfermedad de Fabry/terapia , Enfermedad de Fabry/ultraestructura , Humanos , Hidantoínas/uso terapéutico , Infertilidad Masculina/etiología , MasculinoRESUMEN
Fabry's disease is an inborn error of sphingolipid metabolism. The lysosomal hydrolase, alpha-galactosidase, is deficient. The full spectrum of symptoms (diffuse angiokeratoma, alpha-galactosidase deficiency) is only seen in males, who are always hemizygous. The heterozygous females may be asymptomatic and the enzyme activity can be normal. Such a case is reported. The diagnosis of this case was made by electron microscopic findings of the characteristic cellular lipid-inclusions within endothelial, perithelial, smooth muscle, and nerve sheath cells. The electron microscopic findings are a valuable clue to the diagnosis in these problem cases. The early diagnosis of female conductors is important for genetic counseling.
Asunto(s)
Enfermedad de Fabry/genética , Heterocigoto , Factores de Edad , Diagnóstico Diferencial , Enfermedad de Fabry/ultraestructura , Femenino , Humanos , Microscopía Electrónica , Músculo Liso/ultraestructura , Músculo Liso Vascular/ultraestructura , Vaina de Mielina/ultraestructura , Factores Sexuales , alfa-Galactosidasa/genéticaRESUMEN
Seven patients with Fabry's disease, an x-linked sphingolipid storage disorder, were evaluated for the presence and extent of airway obstruction. All were found to have significant obstruction to airflow. In addition, evaluation of their airway epithelial cells obtained by bronchoscopy demonstrated that these cells contained inclusion bodies consistent with deposits of ceramide trihexoside, suggesting that part of their functional obstruction to airflow may be secondary to intrinsic airway disease. Although all of the study population had evidence of airflow obstruction, the impairment was much worse in those who smoked, implying that even mild cigarette smoking is particularly hazardous to patients with Fabry's disease.
Asunto(s)
Obstrucción de las Vías Aéreas/complicaciones , Enfermedad de Fabry/complicaciones , Adulto , Obstrucción de las Vías Aéreas/fisiopatología , Epitelio/ultraestructura , Enfermedad de Fabry/fisiopatología , Enfermedad de Fabry/ultraestructura , Femenino , Galactosilgalactosilglucosilceramidasa , Humanos , Cuerpos de Inclusión/ultraestructura , Masculino , Persona de Mediana Edad , Alveolos Pulmonares/ultraestructura , Pruebas de Función Respiratoria , Fumar/complicaciones , Relación Ventilacion-PerfusiónAsunto(s)
Gránulos Citoplasmáticos/patología , Enfermedad de Fabry/ultraestructura , Piel/ultraestructura , Adulto , Humanos , Masculino , Pene , MusloRESUMEN
Fabry's disease is a lipid storage disease found in children and adults. The lipid is stored as a myelin-figure-like whorl of membranes in endothelial and smooth muscle cells, myocardium, fibroblasts, and epithelial cells of the glomerulus. The lipid deposits are identifiable by light microscopy, but are much easier to demonstrate by electron microscopy. The disease leads to vascular insufficiency because of narrowing and thrombosis of arteries and arterioles. The resultant vascular insufficiency leads to peripheral neuritis, myocardial infarction, peripheral infarction and cerebral infarction. Corneal clouding due to lipid deposits is also seen. Renal involvement is widespread, but renal failure occurs late.