Anderson-Fabry Disease in Females

Anderson-Fabry disease (AFD) is the second most common lysosomal storage disease. This is an X-linked disorder due to lysosomal enzyme deficiency of a-galac-tosidasae A, that results in accumulation of globotriaosyl-ceramide in various tissues leading to organ damage, and resulting in a variety of cardiovascular, renal, neural, der-matological, psychological signs and symptoms. Despite being X-linked, heterozygous females can suffer from symptoms equally severe as male hemizygotes. This paper presents signs, symptoms, specific diagnostic approach and treatment possibilities of AFD in female patients.

Involvement of the fractalkine pathway in the pathogenesis of childhood hemolytic uremic syndrome

Thrombotic microangiopathy and acute renal failure are cardinal features of postdiarrheal hemolytic uremic syndrome (HUS). These conditions are related to endothelial and epithelial cell damage induced by Shiga toxin (Stx) through the interaction with its globotriaosyl ceramide receptor. However, inflammatory processes contribute to the pathogenesis of HUS by sensitizing cells to Stx fractalkine (FKN), a CX3C transmembrane chemokine expressed on epithelial and endothelial cells upon activation, is involved in the selective migration and adhesion of specific leukocyte subsets to tissues. Here, we demonstrated a selective depletion of circulating mononuclear leukocytes expressing the receptor for FKN (CX3CR1) in patients with HUS. We found a unique phenotype in children with HUS distinct from that seen in healthy, uremic, or infected controls, in which monocytes lost CX3CR1, down-modulated CD62L, and increased CD16. In addition, the CD56dim natural killer (NK) subpopulation was decreased, leading to an altered peripheral CD56dim/CD56bright ratio from 10.0 to 4.5. It is noteworthy that a negative correlation existed between the percentage of circulating CX3CR1+ leukocytes and the severity of renal failure. Finally, CX3CR1+ leukocytes were observed in renal biopsies from patients with HUS. We suggest that the interaction of CX3CR1+ cells with FKN present on activated endothelial cells may contribute to renal injury in HUS.