Fabry's Disease: Alpha-Galactosidase Deficiency

Abstract

The leukocytes of male patients with Fabry's disease are deficient in alpha-galactosidase. The alpha-galactosidase activity in the leukocytes of female carriers of the disease is 15 to 40 percent of the amount present in normal leukocytes. The activities of beta-galactosidase, beta-acetylgalactosaminidase, and beta-acetylglucosaminidase in the leukocytes of affected individuals are normal.

Occurrence of sialidase activity in two distinct and highly homogeneous populations of lysosomes prepared from the brain of developing mouse

“…32.1.22) was deter. mined by the fluorimetric ~rocedure or Kint [15]; the plasma membrarte rnarker ~'.nucleotidase (E.C, 3.1 3,5) by the method of lpata [16], as perfected by Melntosh and Plummer [171', the mitochondrial marker succinate dehydrogenase (E.C. 1.1.1.49~ by the method of Oennmgton [18]; the cytosol markers lactate dehydrogenase (E,C.…”

Questioning the Pathogenic Role of the GLA p.Ala143Thr “Mutation” in Fabry Disease: Implications for Screening Studies and ERT

“…As a result, glycosphingolipids, mainly globotriaosylceramide (Gb-3), accumulate in different cells throughout the body, ultimately resulting in organ failure (Kint 1970;Brady et al 1967). Classical FD has been described as a multisystem disease predominantly presenting in males with angiokeratoma, hypohidrosis, and acroparesthesia in childhood, followed by renal failure, left ventricular hypertrophy, stroke, and premature death in the fourth and fifth decade of life.…”

Highly Versatile Polyelectrolyte Complexes for Improving the Enzyme Replacement Therapy of Lysosomal Storage Disorders

“…45 Following safety concerns for future in vivo applications, we investigated the potential toxicity of the PECs on HeLa, a routinely used cell line for cytotoxicity evaluation, and HMEC-1 cells, as vascular endothelial cells represent the main target for therapeutics in Fabry disease. [19][20][21] For PEC concentrations up to 5.5 µg mL -1 cell viability is not significantly affected, maintained around 80% (Figure 2). Besides, hemolysis of the PECs suspensions was always lower than 1% when tested against mouse RBC (Figure 3), clearly below the 5% value considered as the toxicity threshold.…”

“…Its deficiency causes the Fabry disease, resulting in the accumulation of Gb3 in the lysosomes of various cells and tissues, mainly at the vascular endothelium. [19][20][21] Therefore, endothelial cells (EC) represent a main target for therapeutical intervention in Fabry disease. Target determinants like E-selectin, VCAM-1, ICAM-1 and integrins like α v β 3 and α v β 5 with expression restricted to EC and upregulated during inflammation or angiogenesis, may help to achieve specific and safe delivery of drugs into EC subsets involved in diseases, thereby improving pharmacological efficacy.…”