Article

Fabry Registry. 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: 2.63). 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.

0 Followers
 · 
21 Reads
  • Source
    • "It was observed that in some females, the X chromosome inactivation is not random in all tissues but some of them show a skewed inactivation to the wild type X chromosome or the mutated one — phenomenon that, still today, is without an explanation (Echevarria et al., 2015). This results in a great clinical heterogeneity ranging from the absence of the manifestations to a severity comparable to the one of the males affected by Fabry disease (Whybra et al., 2001;MacDermot et al., 2001;Wilcox et al., 2008). The missense mutation described in this article is also responsible of Fabry phenotype. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Fabry disease is a metabolic and lysosomal storage disorder caused by the functional defect of the α-galactosidase A enzyme; this defect is due to mutations in the GLA gene, that is composed of seven exons and is located on the long arm of the X-chromosome (Xq21-22). The enzymatic deficit is responsible for the accumulation of glycosphingolipids in lysosomes of different cellular types, mainly in those ones of vascular endothelium. It consequently causes a cellular and microvascular dysfunction. In this paper, we described five novel mutations in the GLA gene, related to absent enzymatic activity and typical manifestations of Fabry disease. We identified three mutations (c.846_847delTC, p.E341X and p.C382X) that lead to the introduction of a stop codon in position 297, 341 and 382. Moreover we found a missense mutation (p.R227P) in the exon 5 of the GLA gene and a single point mutation (c.639+5G>T) occurring five base pairs beyond the end of the exon 4. These mutations have never been found in our group of healthy control subjects >2300. The studied patients presented some clinical manifestations, such as cornea verticillata, hypo-anhidrosis, left ventricular hypertrophy, cerebrovascular disorders and renal failure, that, considering the null enzymatic activity, suggest that the new mutations reported here are related to the classic form of Fabry disease. The identification of novel mutations in patients with symptomatology referable to FD increases the molecular knowledge of the GLA gene and it gives to clinicians an important support for the proper diagnosis of the disease.
    Full-text · Article · Dec 2015 · Gene
  • Source
    • "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). "

    Full-text · Article · Feb 2015 · Molecular Genetics and Metabolism
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Jan 2015
Show more