Nakao S, Takenaka T, Maeda M, Kodama C, Tanaka A, Tahara M, Yoshida A, Kuriyama M, Hayashibe H, Sakuraba H
First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Japan.
N Engl J Med. 1995 Aug 3;333(5):288-93. doi: 10.1056/NEJM199508033330504.
Fabry's disease is considered very rare. Left ventricular hypertrophy is one of the common manifestations in adults with classic hemizygous disease. Recently, several cases of an atypical variant of hemizygous Fabry's disease, with manifestations limited to the heart, have been reported. Therefore, we assessed the incidence of hemizygosity for Fabry's disease among male patients with left ventricular hypertrophy.
We measured plasma alpha-galactosidase activity in 230 consecutive male patients with left ventricular hypertrophy. Clinical manifestations were assessed, endomyocardial biopsies were performed, and the patients were screened for mutations in the alpha-galactosidase gene.
Seven of the 230 patients with left ventricular hypertrophy (3 percent) had low plasma alpha-galactosidase activity (0.4 to 1.2 nmol per hour per milliliter; 4 to 14 percent of the mean value in normal controls). These seven unrelated patients, ranging in age from 55 to 72 years, did not have angiokeratoma, acroparesthesias, hypohidrosis, or corneal opacities, which are typical manifestations of Fabry's disease. Endomyocardial biopsy was performed in five patients and revealed marked sarcoplasmic vacuolization in all five. Samples from four patients were examined by electron microscopy and revealed typical lysosomal inclusions with a concentric lamellar configuration in all four. Two patients had novel missense mutations in exon 1 (Ala20Pro) and exon 6 (Met296lle). The remaining five had no mutations in the coding region of the alpha-galactosidase gene, but the amounts of the alpha-galactosidase messenger RNA were markedly lower than normal.
Seven unrelated patients with atypical variants of hemizygous Fabry's disease were found among 230 men with left ventricular hypertrophy (3 percent). Fabry's disease should be considered as a cause of unexplained left ventricular hypertrophy.
法布里病被认为非常罕见。左心室肥厚是经典半合子型疾病成年患者的常见表现之一。最近，有几例半合子型法布里病非典型变异型的病例报告，其表现仅限于心脏。因此，我们评估了左心室肥厚男性患者中法布里病半合子状态的发生率。
我们测定了230例连续的左心室肥厚男性患者的血浆α-半乳糖苷酶活性。评估临床表现，进行心内膜活检，并对患者进行α-半乳糖苷酶基因突变筛查。
230例左心室肥厚患者中有7例（3%）血浆α-半乳糖苷酶活性较低（每小时每毫升0.4至1.2纳摩尔；为正常对照平均值的4%至14%）。这7例无亲缘关系的患者年龄在55至72岁之间，没有血管角质瘤、肢端感觉异常、少汗或角膜混浊等法布里病的典型表现。对5例患者进行了心内膜活检，所有5例均显示明显的肌浆空泡化。对4例患者的样本进行电子显微镜检查，所有4例均显示典型的同心层状溶酶体包涵体。2例患者在外显子1（Ala20Pro）和外显子6（Met296lle）中有新的错义突变。其余5例在α-半乳糖苷酶基因编码区无突变，但α-半乳糖苷酶信使核糖核酸的量明显低于正常水平。
在230例左心室肥厚男性患者中发现了7例半合子型法布里病非典型变异型患者（3%）。法布里病应被视为不明原因左心室肥厚的病因之一。
