ABSTRACT
Fabry disease is a progressive X-linked disorder of glycosphingolipid metabolism caused by a deficiency of the alpha-galactosidase lysosomal enzyme. The partial or complete deficiency of the lysosomal enzyme leads to an accumulation of neutral glycosphingolipids in the vascular endothelium and visceral tissues throughout the body. In the heart, glycosphingolipids deposition causes progressive left ventricular hypertrophy (LVH). We report a case of Fabry disease which was suspected based upon two-dimensional echocardiographic finding of LVH. A 44-year-old man was admitted to evaluation of aggravated exertional dyspnea of two weeks duration. He had been diagnosed with end-stage renal disease of unknown etiology at age 41 followed by renal transplantation that year. He had been treated with oral immunosuppressive agents. On hospital day two, transthoracic echocardiography revealed concentric LVH. Left ventricular systolic function was preserved but diastolic dysfunction was present. Fabry disease was confirmed by demonstration of a low plasma alpha-galactosidase A (alpha-Gal A) activity. Analysis of genomic DNA showed alpha-Gal A gene mutation. The patient was diagnosed with Fabry disease.
Subject(s)
Humans , alpha-Galactosidase , Cardiomyopathies , DNA , Dyspnea , Echocardiography , Endothelium, Vascular , Fabry Disease , Genes, vif , Glycosphingolipids , Heart , Hypertrophy, Left Ventricular , Immunosuppressive Agents , Kidney Failure, Chronic , Kidney Transplantation , Neutral Glycosphingolipids , PlasmaABSTRACT
Fabry disease, angiokeratoma corporis diffusum, is a rare X-linked inborn error of glycosphingolipid metabolism due to the lack of the lysosomal enzyme, alpha-galactosidase A, resulting in a progressive deposition of specific neutral glycosphingolipids within the lysosomes of endothelial and smooth muscle cells of the cardiovascular and renal systems predominantly. We reported a case of Fabry disease, following renal biopsy for the investigation of proteinuria(Creatinine clearance 87.28 mL/min/1.73, serum creatinine 1.1 mg/dL, 24-hour urine protein 1,125 mg, 24-hour urine creatinine 1,382 mg). The patient was 46 year old male. He had experienced anterior chest pain regarded as angina pectoris for a few years. A 12- lead electrocardiogram was abnormal(T-wave inversion in II, III, AVF, and V3-V6), but echocardiography and coronary angiography revealed no abnormal. Kidney biopsy findings showed lamella inclusion bodies on electron microscopy, which are typical finding of Fabry disease. The patient is followed at O.P.D without any significant complaints for 18 months after diagnosis of Fabry disease.
Subject(s)
Humans , Male , Middle Aged , alpha-Galactosidase , Angina Pectoris , Biopsy , Chest Pain , Coronary Angiography , Creatinine , Diagnosis , Echocardiography , Electrocardiography , Fabry Disease , Inclusion Bodies , Kidney , Lysosomes , Metabolism , Microscopy, Electron , Myocytes, Smooth Muscle , Neutral Glycosphingolipids , ProteinuriaABSTRACT
Fabry's disease, angiokeratoma corporis diffusum, is a rare X-linked inborn error of glycosphingolipid metabolism due to the lack of the lysosomal enzyme, alpha-galactosidase A, resulting in a progressive intracellular deposition of neutral glycosphingolipids in various tissues, including the dorsal root ganglia, autonomic nervous system, vascular endothelial, and smooth muscle cells. Clinical manifestations of Fabry's disease result predominantly from the progressive deposition of globotriaocylceramide in the nervous system or vascular endothelium, and are characterized by acro-paresthesia, angiokeratoma, corneal opacity, TIA or stroke, ischemic heart disease, and renal failure. We report a case of a 19-year-old man presenting with a 12-year history of severe distal pain, acroparesthesia, short stature, and delayed puberty. An enzymatic assay disclosed substantially diminished alpha-galactosidase A activity and an electron microscopy of the peripheral nerve showed lipid inclusions which were composed of concentrically laminated, ovoid osmiophilic bodies in the perineural fibroblast and endothelial cells. These findings are typical of Fabry's disease and additional genetic study revealed deletion mutation(TTAG) at the 6th exon of the alpha-galactosidase A gene, which is a novel mutation that had never been reported in literatures. Symptomatic treatment with carbamazepine and clonazepam was tried with a good response.
Subject(s)
Humans , Young Adult , alpha-Galactosidase , Angiokeratoma , Autonomic Nervous System , Carbamazepine , Clonazepam , Corneal Opacity , Endothelial Cells , Endothelium, Vascular , Enzyme Assays , Exons , Fabry Disease , Fibroblasts , Ganglia, Spinal , Metabolism , Microscopy, Electron , Myocardial Ischemia , Myocytes, Smooth Muscle , Nervous System , Neutral Glycosphingolipids , Peripheral Nerves , Puberty, Delayed , Renal Insufficiency , StrokeABSTRACT
Fabry's disease is a rare, inborn error, sex-linked disorder of glycosphingolipid metabolism with death occurring from myocardial or renal involvement at 4th or 5th decades. The primary metabolic defect lies in the deficient tissue activity of the enzyme alpha-galactosidase A which results in progressive accumulation of the specific neutral glycosphingolipids, cerebroside dihexoside(CDH) and cerebroside triihexoside(CTH), within the lysosomes of endothelial, perithelial and smooth muscle cells of the cardiovascular and renal systems predominantly. Clinical manifestations are sequelae of the anatomic and physiologic alterations produced by the progressive deposition of glycosphingolipid in the tissues. We report the first case of successful renal transplantation in a patient with Fabry's disease in Korea. The patient was a 33-year-old male. Fabry's disease was confirmed by measurement of serum alpha- galactosidase level and renal biopsy. Biopsy finding showed lamellar inclusion bodies on electron microscopy. Galactosidase activity was also markedly decreased. He has been well for 49 months.
Subject(s)
Adult , Humans , Male , alpha-Galactosidase , Biopsy , Fabry Disease , Galactosidases , Inclusion Bodies , Kidney Transplantation , Korea , Lysosomes , Metabolism , Microscopy, Electron , Myocytes, Smooth Muscle , Neutral Glycosphingolipids , TransplantationABSTRACT
Fabry's disease is a rare, inborn error, sex-linked disorder of glycosphingolipid metabolism with death occurring from myocardial or renal involvement at 4th or 5th decades. The primary metabolic defect lies in the deficient tissue activity of the enzyme alpha-galactosidase A which results in progressive accumulation of the specific neutral glycosphingolipids, cerebroside dihexoside(CDH) and cerebroside triihexoside(CTH), within the lysosomes of endothelial, perithelial and smooth muscle cells of the cardiovascular and renal systems predominantly. Clinical manifestations are sequelae of the anatomic and physiologic alterations produced by the progressive deposition of glycosphingolipid in the tissues. We report the first case of successful renal transplantation in a patient with Fabry's disease in Korea. The patient was a 33-year-old male. Fabry's disease was confirmed by measurement of serum alpha- galactosidase level and renal biopsy. Biopsy finding showed lamellar inclusion bodies on electron microscopy. Galactosidase activity was also markedly decreased. He has been well for 49 months.