Clinical characteristics and mutation spectrum of GLA in Korean patients with Fabry disease by a nationwide survey: Underdiagnosis of late-onset phenotype

• Published in: Medicine (Baltimore) 2017-07, Vol.96 (29), p.e7387-e7387
• Main Authors: Choi, Jin-Ho, Lee, Beom Hee, Heo, Sun Hee, Kim, Gu-Hwan, Kim, Yoo-Mi, Kim, Dae-Seong, Ko, Jung Min, Sohn, Young Bae, Hong, Yong Hee, Lee, Dong-Hwan, Kook, Hoon, Lim, Han Hyuk, Kim, Kyung Hee, Kim, Woo-Shik, Hong, Geu-Ru, Kim, Su-Hyun, Park, Sang Hyun, Kim, Chan-Duck, Kim, So Mi, Seo, Jeong-Sook, Yoo, Han-Wook
• Format: Article
• Language: English
• Subjects: Adolescent; Age of Onset; Aged; alpha-Galactosidase - genetics; Child; Child, Preschool; Diagnostic Errors; Enzyme Replacement Therapy; Fabry Disease - diagnosis; Fabry Disease - drug therapy; Fabry Disease - epidemiology; Fabry Disease - genetics; Female; Genetic Association Studies; Humans; Incidence; Infant, Newborn; Male; Middle Aged; Mutation; Neonatal Screening; Observational Study; Phenotype; Republic of Korea - epidemiology; Surveys and Questionnaires; Treatment Outcome; Young Adult
• ISSN: 0025-7974; 1536-5964
• DOI: 10.1097/MD.0000000000007387

Fabry disease is a rare X-linked lysosomal storage disorder caused by an α-galactosidase A deficiency. The progressive accumulation of globotriaosylceramide (GL-3) results in life-threatening complications, including renal, cardiac, and cerebrovascular diseases. This study investigated the phenotypic and molecular spectra of GLA mutations in Korean patients with Fabry disease using a nationwide survey.This study included 94 patients from 46 independent pedigrees: 38 adult males, 46 symptomatic females, and 10 pediatric males. Each diagnosis was based on an enzyme assay and GLA gene mutation analysis.The mean age at presentation was 24 years (range, 5-65 years); however, the diagnoses were delayed by 21 ± 19 years after the onset of symptoms. Those patients with late-onset Fabry disease were diagnosed by family screening or milder symptoms at a later age. Forty different mutations were identified: 20 missense (50%), 10 nonsense (25%), 8 frameshift (20%), and 2 splice site (5%) mutations. Five of them were novel. IVS4+919G>A (c.936+919 G>A) was not detected among the 6505 alleles via newborn screening using dried blood spots. Enzyme replacement therapy (ERT) was performed in all the males and pediatric patients, whereas 75% of the symptomatic females underwent ERT for 4.2 ± 3.6 years.This study described the demographic data, wide clinical spectrum of phenotypes, and GLA mutation spectrum of Fabry disease in Korea. Most of the patients had classical Fabry disease, with a 4 times higher incidence than that of late-onset Fabry disease, indicating an underdiagnosis of mild, late-onset Fabry disease.