PDF(Pubmed)
Abstract：
Fabry disease (FD) is an X-linked, hereditary dysfunction of glycosphingolipid storage caused by mutations in the GLA gene encoding alpha-galactosidase A enzyme. In rare cases, FD may coexist with immunoglobulin A nephropathy (IgAN). We describe a case of concurrent FD, IgAN, and dilated cardiomyopathy-causing mutations in the TTN and BAG3 genes, which has not been reported previously.
A 60-year-old female patient was admitted with a one-week history of facial and lower-limb edema, two-year history of left ventricular hypertrophy and sinus bradycardia, and recurring numbness and pain in three lateral digits with bilateral thenar muscle atrophy. Renal biopsy revealed concurrent FD (confirmed via an alpha-galactosidase A enzyme assay, Lyso-GL-3 quantification, and GLA gene sequencing) and IgAN. Heterozygous mutations in the TTN (c.30,484 C > A;p.P10162T) and BAG3 (c.88 A > G;p.I30V) genes were observed. The patient reported that two of her brothers had undergone kidney transplantation; one died suddenly at 60 years of age, and the other required a cardiac pacemaker. The 35-year-old son of the patient was screened for the GLA gene mutation and found to be positive for the same mutation as the patient. The patient was administered oral losartan (50 mg/day). Enzyme replacement therapy was refused due to financial reasons. Her renal and cardiac functions were stable yet worth closely monitoring during follow-up.
The family history of patients with concurrent heart and renal diseases should be assessed in detail. Genetic testing and histological examinations are essential for diagnosing FD with IgAN.
A 60-year-old female patient was admitted with a one-week history of facial and lower-limb edema, two-year history of left ventricular hypertrophy and sinus bradycardia, and recurring numbness and pain in three lateral digits with bilateral thenar muscle atrophy. Renal biopsy revealed concurrent FD (confirmed via an alpha-galactosidase A enzyme assay, Lyso-GL-3 quantification, and GLA gene sequencing) and IgAN. Heterozygous mutations in the TTN (c.30,484 C > A;p.P10162T) and BAG3 (c.88 A > G;p.I30V) genes were observed. The patient reported that two of her brothers had undergone kidney transplantation; one died suddenly at 60 years of age, and the other required a cardiac pacemaker. The 35-year-old son of the patient was screened for the GLA gene mutation and found to be positive for the same mutation as the patient. The patient was administered oral losartan (50 mg/day). Enzyme replacement therapy was refused due to financial reasons. Her renal and cardiac functions were stable yet worth closely monitoring during follow-up.
The family history of patients with concurrent heart and renal diseases should be assessed in detail. Genetic testing and histological examinations are essential for diagnosing FD with IgAN.
摘要：
背景：法布里病（FD）是X连锁的，由编码α-半乳糖苷酶A酶的GLA基因突变引起的鞘糖脂储存的遗传性功能障碍。在极少数情况下,FD可能与免疫球蛋白A肾病（IgAN）共存。我们描述了并发FD的情况，伊根,以及导致TTN和BAG3基因突变的扩张型心肌病，以前没有报道过。
方法：一名60岁女性患者入院，有一周的面部和下肢水肿史，2年左心室肥厚和窦性心动过缓病史,三指外侧反复出现麻木和疼痛，伴有双侧鱼际肌肉萎缩。肾活检显示并发FD（通过α-半乳糖苷酶A酶测定证实，Lyso-GL-3定量，和GLA基因测序）和IgAN。TTN中的杂合突变（c.30,484C>A；p。P10162T）和BAG3（c.88A>G；p。观察到I30V)基因。病人报告说，她的两个兄弟接受了肾脏移植；一个人在60岁时突然死亡，另一个需要心脏起搏器.对患者的35岁儿子进行了GLA基因突变筛查，发现与患者相同的突变呈阳性。患者口服氯沙坦(50mg/天)。由于经济原因，酶替代疗法被拒绝。她的肾功能和心功能稳定，但在随访期间值得密切监测。
结论：应详细评估并发心脏和肾脏疾病患者的家族史。基因检测和组织学检查对于诊断IgAN型FD至关重要。
方法：一名60岁女性患者入院，有一周的面部和下肢水肿史，2年左心室肥厚和窦性心动过缓病史,三指外侧反复出现麻木和疼痛，伴有双侧鱼际肌肉萎缩。肾活检显示并发FD（通过α-半乳糖苷酶A酶测定证实，Lyso-GL-3定量，和GLA基因测序）和IgAN。TTN中的杂合突变（c.30,484C>A；p。P10162T）和BAG3（c.88A>G；p。观察到I30V)基因。病人报告说，她的两个兄弟接受了肾脏移植；一个人在60岁时突然死亡，另一个需要心脏起搏器.对患者的35岁儿子进行了GLA基因突变筛查，发现与患者相同的突变呈阳性。患者口服氯沙坦(50mg/天)。由于经济原因，酶替代疗法被拒绝。她的肾功能和心功能稳定，但在随访期间值得密切监测。
结论：应详细评估并发心脏和肾脏疾病患者的家族史。基因检测和组织学检查对于诊断IgAN型FD至关重要。
