High incidence of the cardiac variant of Fabry disease revealed by newborn screening in the Taiwan Chinese population.
BACKGROUND
Fabry disease is a treatable lysosomal storage disorder, which is often misdiagnosed or belatedly diagnosed.


RESULTS
To determine the disease incidence in the Taiwan Chinese population, a Fabry disease newborn screening study was initiated. A total of 110 027 newborns were screened by assaying the alpha-galactosidase A (alpha-Gal A) activity using dry blood spots. Low plasma alpha-Gal A activity and presence of a Fabry mutation was demonstrated in 45 neonates (3 females). Eight different mutations were identified, including 3 known missense mutations (R112H, A143T, and R356W), 4 novel missense mutations (G104V, M296L, G360C, and K391T), and one known intronic mutation (IVS4+919G-->A). The IVS4+919G-->A mutation was most common (82% of patients). A total of 20 maternal grandparents of infants harboring this intronic mutation were evaluated by echocardiography, mutation analysis and alpha-Gal A activity assay. The intronic mutation was found in 9 grandfathers and 11 grandmothers. Of these grandparents, 3 grandfathers (33%) but none of the grandmothers had hypertrophic cardiomyopathy. Additionally, 16 males who had been diagnosed with idiopathic hypertrophic cardiomyopathy were screened by mutation analysis and alpha-Gal A activity; 4 (25%) showed deficient plasma alpha-Gal A activity in combination with the intronic mutation.


CONCLUSIONS
We found an unexpected high prevalence of the cardiac variant Fabry mutation IVS4+919G-->A among both newborns (approximately 1 in 1600 males) and patients with idiopathic hypertrophic cardiomyopathy in the Taiwan Chinese population. The early identification of undiagnosed patients allows timely therapeutic intervention providing a better clinical outcome.
Lin
Hsiang-Yu
HY
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Chong
Kah-Wai
KW
Hsu
Ju-Hui
JH
Yu
Hsiao-Chi
HC
Shih
Chun-Che
CC
Huang
Cheng-Hung
CH
Lin
Shing-Jong
SJ
Chen
Chen-Huan
CH
Chiang
Chuan-Chi
CC
Ho
Huey-Jane
HJ
Lee
Pi-Chang
PC
Kao
Chuan-Hong
CH
Cheng
Kang-Hsiang
KH
Hsueh
Chuen
C
Niu
Dau-Ming
DM
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000201:enzymology* / Q000453:epidemiology / Q000209:etiology; D000795:Fabry Disease / Q000150:complications / Q000175:diagnosis / Q000201:enzymology* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015997:Neonatal Screening; D010375:Pedigree; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult; D000519:alpha-Galactosidase / Q000097:blood / Q000235:genetics*
D000519:alpha-Galactosidase