[Show abstract][Hide abstract] ABSTRACT: Fabry disease (FD), an X-linked lysosomal storage disorder, is caused by a reduced activity of the lysosomal enzyme alpha-galactosidase A. The disorder ultimately leads to organ damage (including renal failure) in males and females. However, heterozygous females usually present a milder phenotype with a later onset and a slower progression.
A combined enzymatic and genetic strategy was used, measuring the activity of alpha-galactosidase A and genotyping the alpha-galactosidase A gene (GLA) in dried blood samples (DBS) of 911 patients undergoing haemodialysis in centers across Spain.
GLA alterations were found in seven unrelated patients (4 males and 3 females). Two novel mutations (p.Gly346AlafsX347 and p.Val199GlyfsX203) were identified as well as a previously described mutation, R118C. The R118C mutation was present in 60% of unrelated patients with GLA causal mutations. The D313Y alteration, considered by some authors as a pseudo-deficiency allele, was also found in two out of seven patients.
Excluding the controversial D313Y alteration, FD presents a frequency of one in 182 individuals (0.55%) within this population of males and females undergoing haemodialysis. Moreover, our findings suggest that a number of patients with unexplained and atypical symptoms of renal disease may have FD. Screening programmes for FD in populations of individuals presenting severe kidney dysfunction, cardiac alterations or cerebrovascular disease may lead to the diagnosis of FD in those patients, the study of their families and eventually the implementation of a specific therapy.
BMC Medical Genetics 02/2010; 11:19. DOI:10.1186/1471-2350-11-19 · 2.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bone mass (BMD) may be evaluated by digital X-ray radiogrammetry (DXR) which it is estimated from multiple cortical measures carried out on five regions of interest over a simple hand-forearm X-ray film. We included 168 HD patients (108 men and 60 women; 63 +/- 14 and 66 +/- 12 years old respectively--p < 0.05-) coming from seven HD units in Asturias. We performed a hand-forearm X-ray, an epidemiologic questionnaire and we revised their medical and analytical records. As the normative data we used the measurements of a random sample of 247 subjects from our own population. The prevalence of osteoporosis was 7% and 40% in men and women respectively. BMD was correlated with weight (r = 0.346), time on HD (r = -0.188), time on treatment (r = -0.235). The porosity was correlated with PTH levels.
Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 01/2003; 23 Suppl 2:100-5. · 1.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dialysis patients have bone metabolic disorders and a higher prevalence of fractures, principally peripheral fractures. However, there are few studies focusing on the prevalence of vertebral fractures. Moreover, aortic calcifications are very common and are an independent predictive factor of vascular morbidity and mortality. The objective of this study was to assess the prevalence of vertebral fractures and vascular calcifications in haemodialysis (HD) patients (n = 99), in comparison with a random sample of general population of similar age and from the same geographical area (n = 624) and study their relationship with clinical, biochemical and therapeutical data. The prevalence of vertebral fractures in HD patients and general population was 19.1% and 24.1% respectively (non-significant statistical differences). In both, sexes, the presence of vertebral fractures was positively associated with age, mean maximum Ca, mean maximum CaxP. In women, time in HD was positively associated as well. On the other hand, the prevalence of aortic calcifications was much higher in HD patients (77.9% vs 37.5%, p < 0.001). HD was a risk factor for aortic calcification in women [OR = 7.7 (IC 95% = 2.6-22.9)] as in men [OR = 5 (IC 95% = 1.9-12.9)]. Severe vascular calcifications were more frequent in HD patients, it reached 57.4% compared with 17% of general population (p < 0.001). Both, in women (64.5% vs 13.3% p < 0.001) and in men (51.4% vs 20.9%), respectively (p < 0.001). In conclusion, the prevalence of vertebral fractures was similar in HD patients and in general population. Nevertheless, frequency and severity of aortic calcifications was higher in HD patients.
Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 01/2003; 23 Suppl 2:106-11. · 1.44 Impact Factor