Low frequency of Fabry disease in patients with common heart disease.
Genet Med
; 20(7): 754-759, 2018 07.
Article
en En
| MEDLINE
| ID: mdl-29227985
ABSTRACT
PURPOSE:
To test the hypothesis that undiagnosed patients with Fabry disease exist among patients affected by common heart disease.METHODS:
Globotriaosylceramide in random whole urine using tandem mass spectroscopy, α-galactosidase A activity in dried blood spots, and next-generation sequencing of pooled or individual genomic DNA samples supplemented by Sanger sequencing.RESULTS:
We tested 2,256 consecutive patients 852 women (median age 65 years (19-95)) and 1,404 men (median age 65 years (21-92)). The primary diagnoses were coronary artery disease (n = 994), arrhythmia (n = 607), cardiomyopathy (n = 138), and valvular disease (n = 568). Urinary globotriaosylceramide was elevated in 15% of patients and 15 males had low α-galactosidase A activity. GLA variants found included R118C (n = 2), D83N, and D313Y (n = 7); IVS6-22 C>T, IVS4-16 A>G, IVS2+990C>A, 5'UTR-10 C>T (n = 4), IVS1-581 C>T, IVS1-1238 G>A, 5'UTR-30 G>A, IVS2+590C>T, IVS0-12 G>A, IVS4+68A>G, IVS0-10 C>T, IVS2-81-77delCAGCC, IVS2-77delC. Although the pathogenicity of several of these missense mutations and complex intronic haplotypes has been controversial, none of the patients screened in this study were diagnosed definitively with Fabry disease.CONCLUSION:
This population of patients with common heart disease did not contain a substantial number of patients with undiagnosed Fabry disease. GLA gene sequencing is superior to urinary globotriaosylceramide or α-galactosidase A activity in the screening for Fabry disease.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Fabry
/
Alfa-Galactosidasa
Límite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Genet Med
Asunto de la revista:
GENETICA MEDICA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos