Fabry disease (FD) is an X-linked lysosomal storage disorder due to deficient alpha-galactosidase activity leading to intracellular glycosphingolipid accumulation. Multiple variants have been reported in the GLA gene coding for alpha-galactosidase, and the question of the pathogenicity of rare variants needs to be addressed, especially in patients with mild phenotypes. The patient, a 37-year-old female, presented with a persistent proteinuria after an otherwise uncomplicated first pregnancy. Renal biopsy showed both mild mesangial IgA deposits, and a striking vacuolization of podocytes and tubular cells consistent with Fabry disease. On electron microscopy, discrete but characteristic pseudo-myelinic lamellar inclusions were observed in the podocytes’ lysosomes. A more detailed physical examination revealed an angiokeratoma, and medical history ancient acroparesthesia. There was no cardiac or cerebral involvement of Fabry disease on magnetic resonance imaging. While blood enzymatic activity of alpha-ga lactosidase was normal in this patient, lysoGb3 was elevated (3 N), and a rare heterozygous variant called c.610 T > C was documented in GLA gene. The patient was treated with an ACE inhibitor, with a rapid decrease in proteinuria. After a 5-year follow-up, her renal function has remained normal, with mild proteinuria, and normal cardiac echography. We report and phenotypically describe the first case of a Fabry disease female patient carrying the GLA c.610 T > C variant associated with a renal-predominant clinical presentation.

中文翻译：

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一名女性患者的G.c T 610 T> C变体的第一个表型描述：一种以肾脏为主的法布里病表现。

法布里病（FD）是一种X连锁的溶酶体贮积病，原因是α-半乳糖苷酶活性不足，导致细胞内糖鞘脂积聚。在编码α-半乳糖苷酶的GLA基因中已经报道了多种变体，并且需要解决罕见变体的致病性问题，尤其是在具有轻表型的患者中。该患者为37岁的女性，在原本没有并发症的第一次妊娠后出现了持续性蛋白尿。肾活检显示轻度的系膜IgA沉积，以及与Fabry病相一致的足细胞和肾小管细胞明显空泡化。在电子显微镜下，在足细胞的溶酶体中观察到离散但特征性的假性髓鞘层状夹杂物。更详细的体检发现血管角膜瘤，和医学史古代肢体感觉异常。在磁共振成像中没有法布里氏病的心脏或大脑受累。尽管该患者的α-ga乳糖苷酶的血液酶活性正常，但lysoGb3升高（3 N），并且在GLA基因中记录了罕见的杂合变体c.610 T>C。该患者接受了ACE抑制剂治疗，蛋白尿迅速减少。经过5年的随访，她的肾功能一直保持正常，伴有轻度蛋白尿和心脏超声检查正常。我们报告并表型上描述了第一例携带GLA c.610 T> C变种与肾脏为主的临床表现的法布里病女性患者。尽管该患者的α-ga乳糖苷酶的血液酶活性正常，但lysoGb3升高（3 N），并且在GLA基因中记录了罕见的杂合变体c.610 T>C。该患者接受了ACE抑制剂治疗，蛋白尿迅速减少。经过5年的随访，她的肾功能一直保持正常，伴有轻度蛋白尿和心脏超声检查正常。我们报告并从表型上描述了携带GLA c.610 T> C变体与以肾脏为主的临床表现相关的Fabry病女性患者的第一例。尽管该患者的α-ga乳糖苷酶的血液酶活性正常，但lysoGb3升高（3 N），并且在GLA基因中记录了罕见的杂合变体c.610 T>C。该患者接受了ACE抑制剂治疗，蛋白尿迅速减少。经过5年的随访，她的肾功能一直保持正常，伴有轻度蛋白尿和心脏超声检查正常。我们报告并从表型上描述了携带GLA c.610 T> C变体与以肾脏为主的临床表现相关的Fabry病女性患者的第一例。经过5年的随访，她的肾功能一直保持正常，伴有轻度蛋白尿和心脏超声检查正常。我们报告并从表型上描述了携带GLA c.610 T> C变体与以肾脏为主的临床表现相关的Fabry病女性患者的第一例。经过5年的随访，她的肾功能一直保持正常，伴有轻度蛋白尿和心脏超声检查正常。我们报告并从表型上描述了携带GLA c.610 T> C变体与以肾脏为主的临床表现相关的Fabry病女性患者的第一例。