Department of Nephrology, University of Naples, Federico II, Italy.
BMC Cardiovasc Disord. 2012 Jun 8;12:39. doi: 10.1186/1471-2261-12-39.
Fabry disease (FD) is a hereditary metabolic disorder caused by the partial or total inactivation of a lysosomal hydrolase, the enzyme α-galactosidase A (GLA). This inactivation is responsible for the storage of undegraded glycosphingolipids in the lysosomes with subsequent cellular and microvascular dysfunction. The incidence of disease is estimated at 1:40,000 in the general population, although neonatal screening initiatives have found an unexpectedly high prevalence of genetic alterations, up to 1:3,100, in newborns in Italy, and have identified a surprisingly high frequency of newborn males with genetic alterations (about 1:1,500) in Taiwan.
We describe the case of a 40-year-old female patient who presented with transient ischemic attack (TIA), discomfort in her hands, intolerance to cold and heat, severe angina and palpitations, chronic kidney disease. Clinical, biochemical and molecular studies were performed.
Reported symptoms, peculiar findings in a renal biopsy - the evidence of occasional lamellar inclusions in podocytes and mesangial cells - and left ventricular (LV) hypertrophy, which are considered to be specific features of FD, as well as molecular evaluations, suggested the diagnosis of a classical form of FD.We detected four mutations in the GLA gene of the patient: -10C>T (g.1170C>T), c.370-77_-81del (g.7188-7192del5), c.640-16A>G (g.10115A>G), c.1000-22C>T (g.10956C>T). These mutations, located in promoter and intronic regulatory regions, have been observed in several patients with manifestations of FD. In our patient clinical picture showed a multisystemic involvement with early onset of symptoms, thus suggesting that these intronic mutations can be found even in patients with classical form of FD.
法布瑞氏病（FD）是一种遗传性代谢紊乱疾病，由溶酶体水解酶α-半乳糖苷酶 A（GLA）部分或完全失活引起。这种失活导致未降解的糖脂在溶酶体中蓄积，随后导致细胞和微血管功能障碍。该病的发病率估计在普通人群中为 1:40000，尽管新生儿筛查计划发现意大利新生儿的基因突变发生率异常高，高达 1:3100，而且在台湾发现基因突变的新生儿男性频率惊人地高（约 1:1500）。
我们描述了一位 40 岁女性患者的病例，她表现为短暂性脑缺血发作（TIA）、手部不适、对冷热不耐受、严重心绞痛和心悸、慢性肾脏病。进行了临床、生化和分子研究。
报告的症状、肾脏活检中的特殊发现-偶尔在足细胞和系膜细胞中出现板层包涵体的证据-以及左心室（LV）肥大，这些被认为是 FD 的特异性特征，以及分子评估，提示诊断为经典型 FD。我们在患者的 GLA 基因中检测到四个突变：-10C>T（g.1170C>T）、c.370-77_-81del（g.7188-7192del5）、c.640-16A>G（g.10115A>G）、c.1000-22C>T（g.10956C>T）。这些突变位于启动子和内含子调控区，已在多个表现为 FD 的患者中观察到。在我们的患者中，临床表现为多系统受累，症状早发，因此提示这些内含子突变甚至可以在经典型 FD 患者中发现。
