Fabry disease: Baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry

Abstract

The Fabry Registry is a global observational research platform established to define outcome data on the natural and treated course of this rare disorder. Participating physicians submit structured longitudinal data to a centralized, confidential database. This report describes the baseline demographic and clinical characteristics of the first 1765 patients (54% males (16% aged < 20 years) and 46% females (13% < 20 years)) enrolled in the Fabry Registry. The median ages at symptom onset and diagnosis were 9 and 23 years (males) and 13 and 32 years (females), respectively, indicating diagnostic delays in both sexes. Frequent presenting symptoms in males included neurological pain (62%), skin signs (31%), gastroenterological symptoms (19%), renal signs (unspecified) (17%), and ophthalmological signs (11%). First symptoms in females included neurological pain (41%), gastroenterological symptoms (13%), ophthalmological (12%), and skin signs (12%). For those patients reporting renal progression, the median age at occurrence was 38 years for both sexes, but onset of cerebrovascular and cardiovascular events was later in females (median 43 and 47 years, respectively) than in males (38 and 41 years, respectively). This paper demonstrates that in spite of the considerable burden of disease in both sexes that begins to manifest in childhood or adolescence, the recognition of the underlying diagnosis is delayed by 14 years in males and 19 years in females. The Fabry Registry provides data that can increase awareness of common symptoms in all age groups, as well as insight into treated and untreated disease course, leading to improved recognition and earlier treatment, and possibly to improved outcomes for affected individuals.

Reduction of Plasma Globotriaosylsphingosine Levels After Switching from Agalsidase Alfa to Agalsidase Beta as Enzyme Replacement Therapy for Fabry Disease

“…The optimal dose of agalsidase has long been a matter of debate (Desnick 2004), and identification of the biochemically and clinically most effective dose has been hampered by the slowly progressive nature of FD that lacks reliable, predictive biochemical or clinical surrogate end points. Additionally, the clinical presentation of FD is highly heterogeneous and the timing of symptom onset highly variable (Eng et al 2007;Hopkin et al 2008). There have been no randomized, double-blind trials of patients matched for sex, age, and disease severity to allow a direct comparison of the effectiveness of agalsidase beta and agalsidase alfa at their approved doses (Desnick and Schuchman 2012).…”

A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease

“…4,23,24 However, the onset of major organ involvement (kidney, heart, brain) occurs about 6 -10 years later in women than in men. 15,19,[25][26][27][28][29][30] The burden of disease in women can be substantial. For example, the Mainz Severity Score Index (MSSI) shows that men and women experience a similar impact from Fabry disease, 31 and health-related quality of life is similarly reduced in women and men with Fabry disease.…”

Fabry Liga: Klinikinis Atvejis Ir Literatūros Apžvalga

“…Bū-tent pirmieji simptomai -akroparastezijos, pilvo skausmai prasideda dar vaikystėje-paauglystėje, tačiau nepaisant jų intensyvumo ir sunkumo, dažnai būna priskiriami "augimo" skausmams arba manoma, kad paauglys simptomus simuliuoja [8]. Remiantis Fabry ligos ("Fabry Registry") ir Fabry rezultatų tyrimų ("The Fabry Outcome Survey" -FOS) duomenų bazių surinktais duomenimis, vidutinis amžius, kai atsiranda simptomų ir nustatoma liga, atitinkamai yra 9 ir 23 metai vyrams ir 13 ir 32 metai moterims [10,1]. Klasikiniu atveju vyrams Fabry liga nustatoma 20-50 metų, kai atsiranda specifiškesnių ligos požymių ir simptomų [11].…”

“…Nepaisant išliekančių nesutarimų, bendri rezultatai rodo teigiamą pakaitinės fermentų terapijos poveikį skausmo, širdies ir kraujagyslių sistemos funkcijai, inkstų funkcijos stabilizavimui [26]. Viena naujausių publikacijų paskelbta Brazilijos mokslininkų 2016 m. liepos mėnesį [10]. Mokslininkai atliko sisteminę apžvalgą, kurioje lyginamas fermentų pakaitinės terapijos (Agalzidazės alfa, Agalzidazės beta) ir placebo efektyvumas bei saugumas.…”