| Summary: | 碩士 === 國立陽明大學 === 臨床醫學研究所 === 98 === Fabry disease is an X-linked recessive lysosomal storage disease resulting from deficient α-galactosidase A (α-Gal A) activity. The estimated incidence of Fabry disease is about 1 in 50,000 males. Cardiac variant of Fabry disease is an atypical type of Fabry disease with residual α-Gal A activity. Patients with the cardiac variant mutation present hypertrophic cardiomyopathy (HCM) in their middle age. Previous studies have shown that the incidence of Fabry disease in male subjects with myocardial hypertrophy is around 3% to 4%.
In Taiwan, Fabry disease newborn screening was initiated from January, 2008. Within 24 months, 205,491 neonates were screened by assaying the α-Gal A activity. Out of these neonates, 74 male and 6 female neonates had low α-Gal A activity and carried GLA gene mutation. Eleven different mutations were detected, including 5 novel missense mutations (p.G104V, p.M296L, p.R301L, p.G360C, p.K391T), 4 known missense mutations (p.R112H, p.A143T, p.R356W, p.R363C), one known nonsense mutation (p.S345X) and one known intronic mutation (IVS4 +919 G>A). The IVS4 +919 G>A mutation was noted to be the most common mutation among these neonates (~81%). In pedigree studies, 21 maternal grandmothers and 20 maternal grandfathers had the intronic mutation. Echocardiography results showed that 10 grandfathers (50%) and 2 grandmothers had HCM. Additionally, the plasma α-Gal A activity and GLA mutation in 43 males with idiopathic HCM were screened, and we found 5 (~11%) males had deficiency of α-Gal A in combination with the intronic mutation.
We identified an unexpected high incidence of Fabry disease in Taiwan (~1/1,450 in males). The high percentage of cardiac variant Fabry disease in patients with idiopathic HCM (~11%) suggested that the diagnosis of Fabry disease should be considered in all patients with idiopathic HCM. The early identification of undiagnosed patients allows timely therapeutic intervention, which would provide a better clinical outcome.
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