Abstract:BackgroundFabry disease (FD) is a lysosomal storage disorder resulting in systemic accumulation of globotriaosylceramide resulting in multi-organ dysfunction e.g. cerebral, cardiac, renal and audiologic complications. The audiologic involvement in FD has often been neglected; while not a lethal aspect of the disease, hearing loss can have a significantly negative impact on quality of life.ObjectivesTo investigate baseline hearing status of the Danish Fabry cohort prior to treatment, compared to sex- and age-ex… Show more
“…For the treated patients, baseline audiogram was defined as the most recent audiogram available prior to initiation of Fabry specific treatment. Due to limited data in the non-treated group, longitudinal analysis was only performed in the treated group which has in part been described before concerning other organ assessments [7] , [8] , [9] , [10] , [11] , [12] . Fig.…”
Section: Methodsmentioning
confidence: 99%
“…Previously, we presented the hearing status of the nationwide Danish Fabry cohort prior to treatment [7] . In the present study, we investigated the hearing through 16 years of follow-up of the Danish nationwide cohort.…”
“…For the treated patients, baseline audiogram was defined as the most recent audiogram available prior to initiation of Fabry specific treatment. Due to limited data in the non-treated group, longitudinal analysis was only performed in the treated group which has in part been described before concerning other organ assessments [7] , [8] , [9] , [10] , [11] , [12] . Fig.…”
Section: Methodsmentioning
confidence: 99%
“…Previously, we presented the hearing status of the nationwide Danish Fabry cohort prior to treatment [7] . In the present study, we investigated the hearing through 16 years of follow-up of the Danish nationwide cohort.…”
“…12,13 As adults, kidney dysfunction typically worsens, 11,14 and patients frequently suffer from stroke, 15 cardiovascular disease, 16,17 and hearing loss. 18,19 The decrease in lifespan experienced by Fabry patients is, in large part, caused by cardiac dysfunction and ischemic stroke. 20 Thrombotic events, including stroke and transient ischemic attacks, are a significant burden on patients and occur at a rate 7.1-and 3.1-fold higher than in the general public for male and female Fabry patients, respectively.…”
Section: Introductionmentioning
confidence: 99%
“…During adolescence, additional symptoms frequently manifest, including gastrointestinal distress, 9,10 proteinuria, 11 and angiokeratomas 12,13 . As adults, kidney dysfunction typically worsens, 11,14 and patients frequently suffer from stroke, 15 cardiovascular disease, 16,17 and hearing loss 18,19 . The decrease in lifespan experienced by Fabry patients is, in large part, caused by cardiac dysfunction and ischemic stroke 20 .…”
Fabry disease results from a deficiency of the lysosomal enzyme ⍺-Galactosidase-A (⍺-Gal A) and is estimated to occur in approximately 1:4100 live births. Characteristic of the disease is the accumulation of α-Gal-A substrates, primarily the glycosphingolipids (GSLs) globotriaosylceramide and globotriaosylsphingosine. Thrombotic events are a significant concern for Fabry patients, with strokes contributing to a significant decrease in overall lifespan. Currently, the mechanisms underlying the increased risk of thrombotic events experienced by Fabry patients are incompletely defined. Using a rat model of Fabry disease, we provide an improved understanding of the mechanisms linking GSL accumulation to thrombotic risk. We found that ⍺-Gal A-deficient rats accumulate myeloid-derived leukocytes at sites of GSL accumulation, including in the bone marrow and circulation, and that myeloid-derived leukocyte and megakaryocyte populations were prominent among cell types that accumulated GSLs. In the circulation, ⍺-Gal A-deficient rats had increases in cytokineproducing cell types and a corresponding elevation of pro-inflammatory cytokines.Lastly, circulating platelets from ⍺-Gal A-deficient rats accumulated a similar set of ⍺-Galactosidase-A substrates as was observed in megakaryocytes in the bone marrow, and exhibited increased platelet binding to fibrinogen in microfluidic and flow cytometric assays.
“…Previous studies reported a markedly reduced quality of life (QoL) in FD patients, particularly in conjunction with pains [9], fatigue [10], depression [11], obstructive sleep apnea [12], hearing loss [13], and gastrointestinal symptoms [4]. In this relatively large patients group, we added data such as demographics, social status, clinical parameters, in addition to these manifestations.…”
BackgroundFabry disease (FD) is a rare X-linked lysosomal storage disorder caused by α-galactosidase A (α-Gal A) deficiency. The progressive accumulation of globotriaosylceramide results in life-threatening complications, including renal, cardiac, and cerebrovascular diseases. In order to improve health care of FD-patients, knowledge of its predictors is important. The aim of our study was to evaluate health-related quality of life (HrQol) in FD and to identify its independent determinants by exploring a wide range of demographic, social and clinical parameters.ResultsIn this cross-sectional multicenter study, 124 adult patients with FD were recruited at three specialized European centers in Germany and Switzerland. Demographics, social status and clinical parameters as well as data on HrQol (EQ5D, EQVAS) and depression were collected by means of self-reporting questionnaires. HrQol and its predictors were evaluated by univariate and multivariate regression analyses.Study population consisted of 72 female and 52 male FD patients (median age 48yrs) of whom 87.9% (N=109) were on enzyme replacement therapy (ERT) (68.8% [N= 75] were on agalsidase α and 31.2% [N=34] on agalsidase β). Univariate analysis revealed various factors reducing HrQol, such as age>40 years, classic phenotype, organ involvement (kidney and heart disease, stroke/transient ischemic attack, gastrointestinal disturbances), depression, and burning limb pain. However, only the following factors were identified as independent predictors of decreased HrQol: classic phenotype, kidney and heart disease, stroke/TIA, depression, and burning limb pain. ERT was an independent determinant of increased HrQol.ConclusionsModifiable factors, such as burning limb pain and depression identified as independent predictors of HrQol-deterioration should be addressed in programs aiming to improve HrQol in FD. A multidisciplinary approach is essential in FD-patients since diverse organ involvement prominently compromises HrQol in affected patients. Our findings that the classic phenotype is a strong predictor of HrQol worsening.
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