Fabry's disease is a rare, X-linked disorder of the glycosphingolipid metabolism, in which a partial or total deficiency of a lysosomal alpha(alpha)-galactosidase results in the progressive accumulation of neutral glycosphingolipids with terminal alpha galactose moieties (i.e., cerebroside di- and trihexoside) in most body fluids and tissues. Accumulation of neutral glycosphingolipids occurs within the lysosomes of endothelial, perithelial, and smooth muscle cells of the myocardial and renal systems; to a lesser extent in reticuloendothelial and connective cells of the cornea; and in ganglion and perineural cells of the autonomic nervous system. In Korea, 7 cases of Fabry's disease have been reported. A 29-year-old man with fever and headache had typical skin findings and a family history of Fabry's disease, and it was confirmed through renal biopsy and enzyme assay for alpha-galactosidase. We report a case of Fabry's disease with a review of the literatures reported in Korea.
Adult ; Case Report ; Fabry Disease/pathology* ; Fabry Disease/metabolism ; Fabry Disease/diagnosis ; Human ; Male

BACKGROUND/AIMS: Fabry disease is an X-linked recessive and progressive disease caused by alpha-galactosidase A (alpha-GaL A) deficiency. We sought to assess the prevalence of unrecognized Fabry disease in dialysis-dependent patients and the efficacy of serum globotriaosylceramide (GL3) screening. METHODS: A total of 480 patients of 1,230 patients among 17 clinics were enrolled. Serum GL3 levels were measured by tandem mass spectrometry. Additionally, we studied the association between increased GL3 levels and cardiovascular disease, cerebrovascular disease, or left ventricular hypertrophy. RESULTS: Twenty-nine patients had elevated serum GL3 levels. The alpha-GaL A activity was determined for the 26 patients with high GL3 levels. The mean alpha-GaL A activity was 64.6 nmol/hr/mg (reference range, 45 to 85), and no patient was identified with decreased alpha-GaL A activity. Among the group with high GL3 levels, 15 women had a alpha-GaL A genetics analysis. No point mutations were discovered among the women with high GL3 levels. No correlation was observed between serum GL3 levels and alpha-GaL A activity; the Pearson correlation coefficient was 0.01352 (p = 0.9478). No significant correlation was observed between increased GL3 levels and the frequency of cardiovascular disease or cerebrovascular disease. CONCLUSIONS: Fabry disease is very rare disease in patients with end-stage renal disease. Serum GL3 measurements as a screening method for Fabry disease showed a high false-positive rate. Thus, serum GL3 levels determined by tandem mass spectrometry may not be useful as a screening method for Fabry disease in patients with end stage renal disease.
Adult ; Aged ; Fabry Disease/blood/*diagnosis ; Female ; Humans ; Kidney Failure, Chronic/blood/*therapy ; Male ; Middle Aged ; *Renal Dialysis ; Trihexosylceramides/*blood ; alpha-Galactosidase/genetics/metabolism

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.
Adult ; alpha-Galactosidase ; Biopsy ; Fabry Disease* ; Galactosidases ; Humans ; Inclusion Bodies ; Kidney Transplantation* ; Korea ; Lysosomes ; Male ; Metabolism ; Microscopy, Electron ; Myocytes, Smooth Muscle ; Neutral Glycosphingolipids ; Transplantation

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.
Adult ; alpha-Galactosidase ; Biopsy ; Fabry Disease* ; Galactosidases ; Humans ; Inclusion Bodies ; Kidney Transplantation* ; Korea ; Lysosomes ; Male ; Metabolism ; Microscopy, Electron ; Myocytes, Smooth Muscle ; Neutral Glycosphingolipids ; Transplantation

Fabry's disease is an X-linked lysosomal storage disorder caused by abnormalities in the alpha-galactosidase A (GLA) gene, which leads to a GLA deficiency and to the intracellular deposition of globotriaosylceramide (Gb3) within vascular endothelium and other tissues. It manifests as progressive multiple organ dysfunctions caused by the deposition of Gb3. On the other hand, congenital agammaglobulinemia is usually caused by mutations in Bruton's tyrosine kinase (Btk) gene with X-linked dominence, suppresses B cell maturation, and causes recurrent pyogenic infections. In former reports, the distance between the loci in the Xq22 region of the human X chromosome was found to be about 69 kilobases. A 23-yr-old man diagnosed with congenital agammaglobulinemia at age 5, showed typical clinical and laboratory and histopathological findings of Fabry's disease. The genetic basis of this combination of the two syndromes was studied in this patient. Here, we report a case of Fabry's disease with congenital agammaglobulinemia.
Adult ; Agammaglobulinemia/congenital/*genetics/pathology ; Chromosomes, Human, X ; Fabry Disease/diagnosis/*genetics ; Humans ; Kidney/pathology ; Male ; Microscopy, Electron ; Sequence Analysis, DNA ; Skin/pathology ; alpha-Galactosidase/genetics/metabolism

Fabry disease (FD) is an X-linked, recessively inherited, rare, progressive, disorder of glycosphingolipid metabolism affecting multiple organs resulting in organ dysfunction. It is rare to find only one FD affected subject with a de novo mutation. Here we report a case of a 41-year-old Asian male diagnosed with de novo FD. Comprehensive ophthalmological evaluation was performed using slit lamp, color fundus photography, optical coherence tomography, fluorescein angiography, and indocyanine green angiography. On slit lamp examination, cornea verticillata and slightly tortuous, and aneurysmal dilatation of inferior bulbar conjunctival vessels were observed. Other imaging modalities showed unremarkable findings. Cornea verticillata and inferior bulbar conjunctival vascular abnormalities may be detected earlier than other ocular abnormalities in de novo FDs like hereditary FDs.
Adult ; Aneurysm ; Angiography ; Asian Continental Ancestry Group ; Cornea ; Dilatation ; Fabry Disease ; Fluorescein Angiography ; Humans ; Indocyanine Green ; Male ; Metabolism ; Photography ; Slit Lamp ; Tomography, Optical Coherence

Fabry disease is an X-linked inborn error of glycosphingolipid catabolism that results from mutations in the gene encoding the alpha-galactosidase A (GLA) enzyme. We have identified 15 distinct mutations in the GLA gene in 13 unrelated patients with classic Fabry disease and 2 unrelated patients with atypical Fabry disease. Two of the identified mutations were novel (i.e., the D231G missense mutation and the L268delfsX1 deletion mutation). This study evaluated the effects of the chemical chaperones 1-deoxygalactonojirimycin (DGJ) on the function of GLA in vitro, in cells containing missense mutations in the GLA gene. Nine missense and a nonsense mutations, including one novel mutation were cloned into mammalian expression vectors. After transient expression in COS-7 cells, GLA enzyme activity and protein expression were analyzed using fluorescence spectrophotometry and Western blot analysis, respectively. DGJ enhanced GLA enzyme activity in the M42V, I91T, R112C and F113L mutants. Interestingly, the I91T and F113L mutations are associated with the atypical form of Fabry disease. However, DGJ treatment did not have any significant effect on the GLA enzyme activity and protein expression of other mutants, including C142W, D231G, D266N, and S297F. Of note, GLA enzyme activity was not detected in the novel mutant (i.e., D231G), although protein expression was similar to the wild type. In the absence of DGJ, the E66Q mutant had wild-type levels of GLA protein expression and approximately 40% GLA activity, indicating that E66Q is either a mild mutation or a functional single nucleotide polymorphism (SNP). Thus, the results of this study suggest that the chemical chaperone DGJ enhances GLA enzyme activity and protein expression in milder mutations associated with the atypical form of Fabry disease.
1-Deoxynojirimycin/*analogs & derivatives/metabolism ; Adolescent ; Adult ; Animals ; Asian Continental Ancestry Group/*genetics ; COS Cells ; Cercopithecus aethiops ; Fabry Disease/*enzymology/genetics ; Gene Expression ; Humans ; Male ; Middle Aged ; Mutation ; Young Adult ; alpha-Galactosidase/*genetics/*metabolism

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.
alpha-Galactosidase ; Angina Pectoris ; Biopsy* ; Chest Pain ; Coronary Angiography ; Creatinine ; Diagnosis ; Echocardiography ; Electrocardiography ; Fabry Disease* ; Humans ; Inclusion Bodies ; Kidney ; Lysosomes ; Male ; Metabolism ; Microscopy, Electron ; Middle Aged ; Myocytes, Smooth Muscle ; Neutral Glycosphingolipids ; Proteinuria*

We report a new α-Galactosidase A (αGal-A) mutation in a 39-year-old Korean born, male Fabry disease patient. Fabry disease is a devastating, progressive inborn error of metabolism caused by X-linked genetic mutations. In this case, the first clinical symptom to occur was in childhood consisting of a burning pain originating in the extremities then radiating inwards to the limbs. This patient also stated to have ringing in his ears, angiokeratomas on his trunk, and cornea verticillata. He visited an outpatient cardiologist due to intermittent and atypical chest discomfort at the age of 39. Electrocardiographic and echocardiographic examination showed left ventricular hypertrophy. A physical examination revealed proteinuria without hematuria. The patient's plasma αGal-A activity was markedly lower than the mean value of the controls. After genetic counseling and obtaining written informed consent, we identified one hemizygous mutation in exon 4 of galactosidase alpha, c.617T>C (p.Leu206 Pro). He was eventually diagnosed as having Fabry disease.
Adult ; Angiokeratoma ; Burns ; Cornea ; Ear ; Echocardiography ; Electrocardiography ; Exons ; Extremities ; Fabry Disease* ; Galactosidases ; Genetic Counseling ; Hematuria ; Humans ; Hypertrophy, Left Ventricular ; Informed Consent ; Male ; Metabolism ; Outpatients ; Physical Examination ; Plasma ; Proteinuria ; Thorax

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.
alpha-Galactosidase ; Angiokeratoma ; Autonomic Nervous System ; Carbamazepine ; Clonazepam ; Corneal Opacity ; Endothelial Cells ; Endothelium, Vascular ; Enzyme Assays ; Exons* ; Fabry Disease* ; Fibroblasts ; Ganglia, Spinal ; Humans ; Metabolism ; Microscopy, Electron ; Myocardial Ischemia ; Myocytes, Smooth Muscle ; Nervous System ; Neutral Glycosphingolipids ; Peripheral Nerves ; Puberty, Delayed ; Renal Insufficiency ; Stroke ; Young Adult