Abstract
Background Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease, caused by defects of the alpha-galactosidase A (GLA) gene. AFD can affect the heart, brain, kidney, eye, skin, peripheral nerves, and gastrointestinal tract. Cardiology (hypertrophic cardiomyopathy), neurology (cryptogenic stroke), and nephrology (end-stage renal failure) screening studies suggest the prevalence of GLA variants is 0.62%, with diagnosis confirmation in 0.12%. 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1037-1050 |
| Number of pages | 14 |
| Journal | Journal of the American College of Cardiology |
| Volume | 68 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Sep 6 2016 |
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Keywords
- biochemical
- family screening
- GLA
- MOGE(S) classification
- multidisciplinary evaluation
- α-Gal
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Genetic Screening of Anderson-Fabry Disease in Probands Referred From Multispecialty Clinics. / 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, Gian Pietro; 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.
In: Journal of the American College of Cardiology, Vol. 68, No. 10, 06.09.2016, p. 1037-1050.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetic Screening of Anderson-Fabry Disease in Probands Referred From Multispecialty Clinics
AU - Favalli, Valentina
AU - Disabella, Eliana
AU - Molinaro, Mariadelfina
AU - Tagliani, Marilena
AU - Scarabotto, Anna
AU - Serio, Alessandra
AU - Grasso, Maurizia
AU - Narula, Nupoor
AU - Giorgianni, Carmela
AU - Caspani, Clelia
AU - Concardi, Monica
AU - Agozzino, Manuela
AU - Giordano, Calogero
AU - Smirnova, Alexandra
AU - Kodama, Takahide
AU - Giuliani, Lorenzo
AU - Antoniazzi, Elena
AU - Borroni, Riccardo G.
AU - Vassallo, Camilla
AU - Mangione, Filippo
AU - Scelsi, Laura
AU - Ghio, Stefano
AU - Pellegrini, Carlo
AU - Zedde, Marialuisa
AU - Fancellu, Laura
AU - Sechi, Gian Pietro
AU - Ganau, Antonello
AU - Piga, Stefania
AU - Colucci, Annarita
AU - Concolino, Daniela
AU - Di Mascio, Maria Teresa
AU - Toni, Danilo
AU - Diomedi, Marina
AU - Rapezzi, Claudio
AU - Biagini, Elena
AU - Marini, Massimiliano
AU - Rasura, Maurizia
AU - Melis, Maurizio
AU - Nucera, Antonia
AU - Guidetti, Donata
AU - Mancuso, Michelangelo
AU - Scoditti, Umberto
AU - Cassini, Pamela
AU - Narula, Jagat
AU - Tavazzi, Luigi
AU - Arbustini, Eloisa
PY - 2016/9/6
Y1 - 2016/9/6
N2 - Background Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease, caused by defects of the alpha-galactosidase A (GLA) gene. AFD can affect the heart, brain, kidney, eye, skin, peripheral nerves, and gastrointestinal tract. Cardiology (hypertrophic cardiomyopathy), neurology (cryptogenic stroke), and nephrology (end-stage renal failure) screening studies suggest the prevalence of GLA variants is 0.62%, with diagnosis confirmation in 0.12%. 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.
AB - Background Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease, caused by defects of the alpha-galactosidase A (GLA) gene. AFD can affect the heart, brain, kidney, eye, skin, peripheral nerves, and gastrointestinal tract. Cardiology (hypertrophic cardiomyopathy), neurology (cryptogenic stroke), and nephrology (end-stage renal failure) screening studies suggest the prevalence of GLA variants is 0.62%, with diagnosis confirmation in 0.12%. 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.
KW - biochemical
KW - family screening
KW - GLA
KW - MOGE(S) classification
KW - multidisciplinary evaluation
KW - α-Gal
UR - http://www.scopus.com/inward/record.url?scp=84994663269&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84994663269&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2016.05.090
DO - 10.1016/j.jacc.2016.05.090
M3 - Article
AN - SCOPUS:84994663269
VL - 68
SP - 1037
EP - 1050
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
SN - 0735-1097
IS - 10
ER -