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Females with Fabry disease frequently have major organ involvement: Lessons from the Fabry Registry

Medical Genetics Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd. SSB, Los Angeles, CA 90048, USA.
Molecular Genetics and Metabolism (Impact Factor: 2.83). 02/2008; 93(2):112-28. DOI: 10.1016/j.ymgme.2007.09.013
Source: PubMed

ABSTRACT Fabry disease (FD) is an X-linked lysosomal storage disease caused by alpha-galactosidase A deficiency. The Fabry Registry is a global clinical effort to collect longitudinal data on FD. In the past, most "carrier" females were usually thought to be clinically unaffected. A systematic effort has been made to enroll all FD females, regardless of symptomology. Of the 1077 enrolled females in the Registry, 69.4% had symptoms and signs of FD. The median age at symptom onset among females was 13 years, and even though 84.1% had a positive family history, the diagnosis was not made until a median age of 31 years. Twenty percent experienced major cerebrovascular, cardiac, or renal events, at a median age of 46 years. Among adult females with estimated glomerular filtration rate (eGFR) data (N=638), 62.5% had an eGFR <90 ml/min/1.73 m2 and 19.0% had eGFR <60 ml/min/1.73 m2. Proteinuria 300 mg/day was present in 39.0% of females, and 22.2% had >1 gram/day. Quality of life (QoL), as measured by the SF-36((R)) survey, was impaired at a later age than in males, but both genders experience significantly impaired QoL from the third decade of life onward. Thus, females with FD have a significant risk for major organ involvement and decreased QoL. Females should be regularly monitored for signs and symptoms of FD, and considered for enzyme replacement therapy.

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    • "study are consistent with Kuratsubo's (2009) suggestion with MPS II subjects that when cognitive abilities are preserved, subjects may display increased psychological symptoms as a result of understanding their disease burden more fully. Research in other LSDs, such as Fabry disease (FD) and Gaucher disease (GD), has likewise documented decreased QOL and begun to examine psychological functioning (Crosbie et al. 2009; Gold et al. 2002; Masek et al. 1999; Packman et al. 2006; Watt et al. 2010; Weinreb et al. 2007; Wilcox et al. 2008). Prevalence estimates of depression in FD range from 15 to 62% (Bolsover et al. 2014; Grewal 1993; Wang et al. 2007), with the largest study (n ¼ 296) reporting 46% (Cole et al. 2007). "
    Molecular Genetics and Metabolism 02/2015; 114(2). DOI:10.1016/j.ymgme.2014.12.008 · 2.83 Impact Factor
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    • "study are consistent with Kuratsubo's (2009) suggestion with MPS II subjects that when cognitive abilities are preserved, subjects may display increased psychological symptoms as a result of understanding their disease burden more fully. Research in other LSDs, such as Fabry disease (FD) and Gaucher disease (GD), has likewise documented decreased QOL and begun to examine psychological functioning (Crosbie et al. 2009; Gold et al. 2002; Masek et al. 1999; Packman et al. 2006; Watt et al. 2010; Weinreb et al. 2007; Wilcox et al. 2008). Prevalence estimates of depression in FD range from 15 to 62% (Bolsover et al. 2014; Grewal 1993; Wang et al. 2007), with the largest study (n ¼ 296) reporting 46% (Cole et al. 2007). "
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    ABSTRACT: Mucopolysaccharidosis type IV (MPSIV), also known as Morquio syndrome, is a progressive genetic condition which predominantly affects skeletal development. Research thus far has focused on physical manifestations, with little attention to psychological characteristics. As a first step in determining the natural occurrence of psychological symptoms in this population, we administered Achenbach measures of psychological functioning (ASEBA ASR and OASR), quality of life (SF-36), and pain severity (BPI) questionnaires to 20 adults with Morquio syndrome. 11/20 subjects (55%) scored within the symptomatic range on at least one or more ASEBA problem scales. These subjects also had higher pain severity scores (p = 0.051) and pain interference scores (p = 0.03) on the BPI. However, subjects with psychological symptoms did not differ significantly on QOL measures from those without psychological symptoms. Overall, subjects scored below the US mean only in physical health QOL (p < 0.001) on the SF-36, not mental health QOL. Implications of this study include the need for greater attention to psychological health in persons with Morquio syndrome, including regular assessment for psychological symptoms in addition to the quality of life measures typically used, as the latter may miss important information. Greater attention to psychological symptoms may help maximize overall health in adults with Morquio syndrome. Comparison with psychological studies on other lysosomal storage diseases suggests these results may be disease specific, rather than the result of living with chronic pain or having an LSD in general.
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    • "Ten publications on time to major complications including stroke, cardiac or renal complications and death were identified (Patel et al 2011; Wilcox et al 2008; Vedder et al 2007b; MacDermot et al 2001a, b; Kobayashi et al 2008; Guffon 2003; Sims et al 2009; Grewal and Barton 1992; Ortiz et al 2010) (supplement Table 2). The proportion of stroke, cardiac and renal complications was higher in untreated men than untreated women and increased with age (Patel et al 2011; Wilcox et al 2008; Vedder et al 2007b; MacDermot et al 2001a, b; Kobayashi et al 2008; Guffon 2003; Sims et al 2009; Grewal and Barton 1992). For adequate comparison of untreated and treated cohorts, cohorts need to be matched or corrected for age and gender. "
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    ABSTRACT: Current available evidence on long-term effectiveness of enzyme replacement therapy (ERT) for Fabry disease is limited. More insight is needed whether ERT effectiveness differs in patients with and without baseline end-organ damage. Through a systematic review, untreated and ERT treated males and females with Fabry disease were compared for main clinical outcomes: renal function, left ventricular mass (LVmass), cerebral white matter lesions (WMLs) and end-organ complications. Through a meta-analysis ERT effectiveness was estimated in different disease stages. Two reviewers assessed quality of the included studies according to guidelines for prognosis research. Data were synthesized using a random effects meta-analysis. Thirty-one studies were systematically reviewed while six studies were included in the meta-analysis. In patients with a GFR > 60 ml/min/1.73 m(2), decline of renal function was similar for treated and untreated patients. Only ERT treated males with a GFR < 60 ml/min/1.73 m(2) had a slower rate of decline in renal function, possibly attributable to anti-proteinuric therapy. Regardless of left ventricular hypertrophy (LVH) at baseline, LVmass remained stable or increased in males despite ERT, however at a slower rate compared to untreated male patients. In ERT treated females with LVH LVmass decreased, and remained stable in females without LVH. WMLs can not be prevented by ERT. Stroke, cardiac and end-stage renal complications develop, though the incidence of new complications seems to be reduced during ERT. ERT is effective in reducing LVH, but has a limited effect on renal function. Improved treatment options are needed for Fabry disease.
    Journal of Inherited Metabolic Disease 02/2014; 37(3). DOI:10.1007/s10545-014-9677-8 · 4.14 Impact Factor
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