Department of Internal Medicine, Chonnam National University Medical School, 160, Baekseo‑ro, Dong‑gu, Gwangju, 61469, Republic of Korea.
Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Korea.
BMC Med Genomics. 2024 Oct 7;17(1):245. doi: 10.1186/s12920-024-02021-3.
Fabry disease is an X-linked lysosomal storage disease caused by the impairment of α-galactosidase A. The complex intronic haplotype (CIH) variants, located in promoter and intronic regulatory lesions, has been found in patients with classical forms of Fabry disease. We present a case of Fabry disease in female monozygotic twins exhibiting the CIH mutation and classical manifestations.
A 61-year-old woman with a history of stroke, carotid artery occlusion, hypertrophic cardiomyopathy, and chronic kidney disease was referred to the nephrology clinic for management of her chronic kidney disease. Her monozygotic twin sister also presented with hypertrophic cardiomyopathy, atrial flutter, carotid stenosis, and proteinuria. Clinical symptoms and a comprehensive family history strongly suggested the presence of Fabry disease. Genetic analysis revealed the presence of 5 variants within a complex intronic haplotype (CIH): c.-10 C > T, c.369 + 990 C > A, c.370 - 81_370-77delCAGCC, c.640-16 A > G, and c.1000-22 C > T. We conducted a review of the patient's previous kidney biopsy findings, which demonstrated the presence of lamellated inclusion bodies in electron microscopy. Remarkably, both the monozygotic twin sister and her son exhibited the same genetic mutation. Enzyme replacement therapy was initiated for the patient. Her kidney function decreased throughout a thorough 2-year follow-up period, while there was a slight decrease in the left ventricular mass index.
This is the first reported case of female monozygotic twins with the CIH variants representing cardiac, cerebrovascular, and renal manifestations suggestive of Fabry disease.
法布瑞病是一种 X 连锁溶酶体贮积病，由α-半乳糖苷酶 A 缺陷引起。复杂内含子单倍型（CIH）变异位于启动子和内含子调控病变中，已在经典型法布瑞病患者中发现。我们报告了一例经典型法布瑞病的女性同卵双胞胎病例，该病例携带有 CIH 突变和经典表现。
一位 61 岁女性，有中风、颈动脉闭塞、肥厚型心肌病和慢性肾脏病病史，因慢性肾脏病就诊于肾病科。她的同卵双胞胎妹妹也表现出肥厚型心肌病、心房颤动、颈动脉狭窄和蛋白尿。临床症状和全面的家族史强烈提示存在法布瑞病。基因分析显示存在 5 个复杂内含子单倍型（CIH）内的变异：c.-10C>T、c.369+990C>A、c.370-81_370-77delCAGCC、c.640-16A>G 和 c.1000-22C>T。我们对患者之前的肾脏活检结果进行了回顾，结果显示电镜下存在层状包涵体。值得注意的是，同卵双胞胎姐妹及其儿子均表现出相同的基因突变。为患者启动了酶替代治疗。在全面的 2 年随访期间，她的肾功能持续下降，而左心室质量指数略有下降。
这是首例报道的 CIH 变异女性同卵双胞胎病例，具有心脏、脑血管和肾脏表现，提示法布瑞病。
