法布里病(FD)是一种X连锁遗传性鞘糖脂代谢紊乱,因此,杂合型女性FD患者表现出高度可变的临床症状,疾病严重程度,和病理结果。这使得诊断女性FD患者非常具有挑战性。一名69岁的日本女性被介绍给肾病学家,以评估蛋白尿。进行肾活检。尽管光学显微镜检查显示大多数肾小球表现出轻微的肾小球异常,然而,在肾小管上皮细胞中明显发现了空泡。在一些足细胞和远端肾小管上皮细胞中检测到球形神经酰胺的免疫荧光染色呈阳性。此外,通过电子显微镜检测到髓鞘样结构(斑马体)。病理结果与FD最为一致。因此,生化和遗传分析证实了女性FD的诊断。酶替代疗法与肾素-血管紧张素醛固酮系统抑制剂和β受体阻滞剂联合进行。病人的家属接受了分析,在病人的孙子身上也检测到了同样的DNA错义突变.将酶替代疗法引入孙子。本案表明,肾活检可有助于正确诊断FD。特别是,在女性FD患者中,仔细检查病理变化是必不可少的,例如,任何类型的肾细胞空泡可能是诊断的线索。
Fabry disease (FD) is an X-linked inherited glycosphingolipid metabolism disorder, therefore, heterozygous female FD patients display highly variable clinical symptoms, disease severity, and pathological findings. This makes it very challenging to diagnosing female patients with FD. A 69-year-old Japanese female was introduced to the nephrologist for the evaluation of proteinuria. A renal biopsy was performed. Although the light microscopic examinations revealed that most of the glomeruli showed minor glomerular abnormalities, however,
vacuolation was apparently found in the tubular epithelial cells. Immunofluorescence staining for globotriaosylceramide was positively detected in some podocytes and distal tubular epithelial cells. In addition, myelin-like structure (zebra body) was detected by electron microscopy. Pathological findings were most consistent with FD. Consequently, biochemical and genetic analysis confirmed the diagnosis of female FD. Enzyme replacement therapy was performed in conjunction with renin-angiotensin aldosterone system inhibitors and beta-blockers. The patient\'s family members received the analysis, and the same DNA missense mutation was detected in the patient\'s grandson. The enzyme replacement therapy was introduced to the grandson. The present
case showed that renal biopsy can contribute towards a correct diagnosis for FD. Particularly, in female FD patients, careful examination of pathological changes is essential, for example,
vacuolation of any type of renal cells may be a clue for the diagnosis.