Naslov
Screening project on Fabry disease

Autori
Vujičić, Božidar ; Malić, Daniela , Orlić, Lidija ; Zaninović-Jurjević, Teodora ; Rački, Sanjin ; Zaputović, Luka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Expert Opinion on Therapeutic Targets. Supplement 1 / - , 2009, 11-12

Skup
International Workshop on Lysosomal Storage Diseases

Mjesto i datum
Lisabon, Portugal, 07.11.2008. - 08.11.2008

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Screening; Fabry disease

Sažetak
Objectives : To screen patients with unexplained hypertrophic cardiomyopathy or end-stage renal disease for Fabry disease using a specially designed questionnaire. Methods : All patients with unexplained hypertrophic cardiomyopathy hospitalized at the Department of Cardiology since 2003 and all patients hospitalized at the Department of Nephrology and Dialysis during 2008 were included in the study. α -Galactosidase A levels were assessed in male patients who fulfilled two or more criteria for Fabry disease according to specially designed cardiological and nephrological questionnaires. Testing was performed at the Biochemical Laboratory of the University Hospital Center in Zagreb, Croatia. The cutoff value for enzyme activity in leukocytes of 50 nmol/h/mg protein was used. Patients with decreased enzyme activity were assessed for the presence of genetic mutations in the GLA gene. Genetic testing was conducted at the Neurobiology Laboratory of the University Hospital in Rostock, Germany. Results : Among 36 patients (12 male) with hypertrophic cardiomyopathy and 223 patients (112 male) with chronic renal disease, 36 and 123 patients, respectively, matched the study criteria. Informed consent was obtained from 21 patients (4 male, 17 female) with hypertrophic cardiomyopathy and 122 patients (72 male, 50 female) with end-stage renal disease. Enzyme activity was assessed in 76 male patients who agreed to be tested and was found to be decreased in 8 patients. Genetic analysis was performed in seven of these patients (one patient declined permission). In one patient, three clinically non-relevant polymorphisms were detected (5’ UTR-30G>A, IVS0-10C>T and IVS6-22C>T). In a second patient who was receiving regular dialysis, the medical consequences of the genetic analysis were unclear (IVS0-10C>T, IVS4-16A>G and IVS6-22C>T). It was not possible to conclude whether the genetic changes resulted in Fabry disease or not. To obtain further data regarding the biological consequences of the mutations found in the second patient, a skin biopsy was performed to assess the presence of globotriaosylceramide in the cells. The results are pending. In the other five patients, genetic analysis revealed no mutations in the GLA gene. Genetic analysis is being performed in the 67 female patients who agreed to further testing. These results are also pending. Conclusion : Fabry disease should be considered as the potential cause of unexplained hypertrophic cardiomyopathy or end-stage renal disease in male and female patients. Screening among patients with hypertrophic cardiomyopathy and patients with chronic renal disease using special questionnaires, followed by assessment of enzyme activity and genetic testing where appropriate, could improve the algorithm for the early diagnosis of Fabry disease.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA