Disease Rarity, Carrier Status, and Gender: A Triple Disadvantage for Women with Fabry Disease

Gibas, Andrea L.; Klatt, R; Johnson, J.; Clarke, Joe T.R.; Katz, Joel

doi:10.1007/s10897-008-9179-7

Cited by 28 publications

(32 citation statements)

References 27 publications

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“…This finding has previously been suggested in published analyses of the Spanish patients in FOS [26,27], all patients in FOS [20] and other studies from different registries [28,29,30,31,32]. Disease rarity, misconceptions about their carrier status and gender have been proposed as the main drivers for the differential access to ERT for females with FD [33]. Evolving knowledge of the natural history of FD and its management with ERT has changed the consideration of heterozygous females from obligate carriers, mostly asymptomatic or with mild disease, to patients with important clinical features and time-dependent disease progression without ERT [30,34,35].…”

Section: Discussionsupporting

confidence: 67%

“…Evolving knowledge of the natural history of FD and its management with ERT has changed the consideration of heterozygous females from obligate carriers, mostly asymptomatic or with mild disease, to patients with important clinical features and time-dependent disease progression without ERT [30,34,35]. Evidence from the literature suggests that females are referred less often for diagnostic interventions and treated less aggressively than males [33]. Furthermore, disparities in treatment between genders have been consistently identified for heart [36] and kidney diseases [31,37], among others [32].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Gender Differences in the Application of Spanish Criteria for Initiation of Enzyme Replacement Therapy for Fabry Disease in the Fabry Outcome Survey

Barba-Romero

Pintos-Morell

2016

IJMS

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Both male/female patients with Fabry disease (FD) may receive enzyme replacement therapy (ERT). Previously published analyses of the Fabry Outcome Survey (FOS; Shire-sponsored) database suggested gender differences in timing of ERT initiation. We assessed alignment of criteria for ERT initiation in the Spanish adult population included in FOS with recommendations of a Spanish national consensus. This retrospective analysis examined baseline clinical data of 88 adults (49 females) enrolled in the FOS database up to August 2014. Thirty-five (39.8%) patients were not receiving ERT: five (12.8%) males and 30 (61.2%) females. Baseline disease severity on the FOS-derived Mainz Severity Score Index was lower in untreated males (median (interquartile range), 0.0 (0.0–1.0)) than treated males (TM; 15.0 (7.5–26.5)), and was similar in untreated and treated females. The percentage of untreated females with at least one criterion for treatment initiation was 76.7% versus 100.0% of treated females (p = 0.0340) and 97.1% (p = 0.0210) of TM. In discordance with Spanish consensus recommendations, a substantial number of females with evidence of FD who might benefit from ERT have not yet initiated treatment. These results suggest unequal gender perceptions with respect to ERT initiation in Spain.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Gender Differences in the Application of Spanish Criteria for Initiation of Enzyme Replacement Therapy for Fabry Disease in the Fabry Outcome Survey

Barba-Romero

Pintos-Morell

2016

IJMS

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“…The estimated incidence of this rare disease is 1:40,000-117,000 live male births [4,7,8]. This figure, however, may be underestimated, as screening performed in newborn males in a Northwestern Italian region showed an incidence of 1 in ~4,000 males [9].…”

Section: Introductionmentioning

confidence: 99%

Expression of the disease on female carriers of X-linked lysosomal disorders: a brief review

Pinto

Vieira

Giugliani

et al. 2010

Orphanet J Rare Dis

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Most lysosomal diseases (LD) are inherited as autosomal recessive traits, but two important conditions have X-linked inheritance: Fabry disease and Mucopolysaccharidosis II (MPS II). These two diseases show a very different pattern regarding expression on heterozygotes, which does not seem to be explained by the X-inactivation mechanism only. While MPS II heterozygotes are asymptomatic in most instances, in Fabry disease most of female carriers show some disease manifestation, which is sometimes severe. It is known that there is a major difference among X-linked diseases depending on the cell autonomy of the gene product involved and, therefore, on the occurrence of cross-correction. Since lysosomal enzymes are usually secreted and uptaken by neighbor cells, the different findings between MPS II and Fabry disease heterozygotes can also be due to different efficiency of cross-correction (higher in MPS II and lower in Fabry disease). In this paper, we review these two X-linked LD in order to discuss the mechanisms that could explain the different rates of penetrance and expressivity observed in the heterozygotes; this could be helpful to better understand the expression of X-linked traits.

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“…Similar to other X-linked diseases, the complications are typically less frequent and more variable in severity in females, [2,3,4] although they can be as severe as in male patients. [5,6] A significant proportion of female patients suffer from important complications, including 40% with clinical renal disease (mainly proteinuria) [7] and about 15% with serious renal events. [2] Fabry disease is associated with significant life expectancy reductions in both sexes.…”

Section: Introductionmentioning

confidence: 99%

Mosaicism of podocyte involvement is related to podocyte injury in females with Fabry disease

Najafian

2015

Molecular Genetics and Metabolism

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Background: Fabry disease. an X-linked deficiency of a-galactosidase A coded by the GLA gene, leads to intracellular globotriaosylceramide (GL-3) accumulation. Although less common than in males, chronic kidney disease, occurs in ,15% of females. Recent studies highlight the importance of podocyte injury in Fabry nephropathy development and progression. We hypothesized that the greater the % of podocytes with active wild-type GLA gene (due to X-inactivation of the mutant copy) the less is the overall podocyte injury.

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Disease Rarity, Carrier Status, and Gender: A Triple Disadvantage for Women with Fabry Disease

Cited by 28 publications

References 27 publications

Gender Differences in the Application of Spanish Criteria for Initiation of Enzyme Replacement Therapy for Fabry Disease in the Fabry Outcome Survey

Gender Differences in the Application of Spanish Criteria for Initiation of Enzyme Replacement Therapy for Fabry Disease in the Fabry Outcome Survey

Expression of the disease on female carriers of X-linked lysosomal disorders: a brief review

Mosaicism of podocyte involvement is related to podocyte injury in females with Fabry disease

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