Genetic Screening of Anderson-Fabry Disease in Probands Referred From Multispecialty Clinics.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Favalli Valentina, Disabella Eliana, Molinaro Mariadelfina, Tagliani Marilena, Scarabotto Anna, Serio Alessandra, Grasso Maurizia, Narula Nupoor, Giorgianni Carmela, Caspani Clelia, Concardi Monica, Agozzino Manuela, Giordano Calogero, Smirnova Alexandra, Kodama Takahide, Giuliani Lorenzo, Antoniazzi Elena, Borroni Riccardo G, Vassallo Camilla, Mangione Filippo, Scelsi Laura, Ghio Stefano, Pellegrini Carlo, Zedde Marialuisa, Fancellu Laura, Sechi GianPietro, Ganau Antonello, Piga Stefania, Colucci Annarita, Concolino Daniela, Di Mascio Maria Teresa, Toni Danilo, Diomedi Marina, Rapezzi Claudio, Biagini Elena, Marini Massimiliano, Rasura Maurizia, Melis Maurizio, Nucera Antonia, Guidetti Donata, Mancuso Michelangelo, Scoditti Umberto, Cassini Pamela, Narula Jagat, Tavazzi Luigi, Arbustini Eloisa
Аннотация
OBJECTIVES: This study sought to expand screening from these settings to include ophthalmology, dermatology, gastroenterology, internal medicine, pediatrics, and medical genetics to increase diagnostic yield and comprehensively evaluate organ involvement in AFD patients.
METHODS: In a 10-year prospective multidisciplinary, multicenter study, we expanded clinical, genetic, and biochemical screening to consecutive patients enrolled from all aforementioned clinical settings. We tested the GLA gene and α-galactosidase A activity in plasma and leukocytes. Inclusion criteria comprised phenotypical traits and absence of male-to-male transmission. Screening was extended to relatives of probands harboring GLA mutations.
RESULTS: Of 2,034 probands fulfilling inclusion criteria, 37 (1.8%) were carriers of GLA mutations. Cascade family screening identified 60 affected relatives; clinical data were available for 4 affected obligate carriers. Activity of α-galactosidase A in plasma and leukocytes was diagnostic in male subjects, but not in female subjects. Of the 101 family members harboring mutations, 86 were affected, 10 were young healthy carriers, and 5 refused clinical evaluation. In the 86 patients, involved organs or organ systems included the heart (69%), peripheral nerves (46%), kidney (45%), eye (37%), brain (34%), skin (32%), gastrointestinal tract (31%), and auditory system (19%). Globotriaosylceramide accumulated in organ-specific and non-organ-specific cells in atypical and classic variants, respectively.
CONCLUSIONS: Screening probands with clinically suspected AFD significantly increased diagnostic yield. The heart was the organ most commonly involved, independent of the clinical setting in which the patient was first evaluated.