Kimball Tamara N, Rivero-García Pamela, Argaiz Eduardo R, Gaytan-Arocha Jorge Eduardo, Uribe Norma Ofelia Uribe, Suárez Juan José Morales
División de Estudios de Posgrado de la Facultad de Medicina, Universidad Nacional Autónoma de, Mexico City, Mexico.
Departamento de Genética, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Mol Genet Genomic Med. 2024 Dec;12(12):e70039. doi: 10.1002/mgg3.70039.
Fabry disease (FD) is a rare lysosomal type 3 disorder with an X-linked inheritance pattern caused by pathogenic variants in the GLA gene. This study aimed to describe the genotype and phenotype of 52 Mexican patients with FD.
We included 12 patients with clinical and molecular diagnosis of FD treated at our institution and 40 FD Mexican patients already reported in the literature.
The most frequent manifestations were acroparesthesias (71.2%), hypohidrosis or anhidrosis (48.1%), heat intolerance (46.2%), and proteinuria (42.3%). Renal and neurological manifestations were more prevalent in males than females. Cardiac involvement included hypertrophic cardiomyopathy and Wolf-Parkinson-White arrhythmia. Cornea verticillata was seen in 14 patients (26.9%) and angiokeratomas in 15 (28.8%). We identified 14 variants in the GLA gene in Mexican patients with FD. We found a novel variant GLA c.122C>G that causes an atypical FD phenotype with predominantly neurological involvement in two unrelated patients, one of them with a forthright clinical and radiological overlap of Multiple Sclerosis and normal biological biomarkers, thus requiring a renal biopsy that helped confirm the diagnosis of FD.
The genotype and phenotype of Mexican patients with FD are similar to other populations. Atypical phenotype of FD, such as the one associated with the novel variant c.122C>G, can be a diagnostic challenge, as it can be mixed up with MS. Our findings confirm the limitations of noninvasive diagnostic methods and the necessity of the renal biopsy when the clinical suspicion of FD is high.
法布里病（FD）是一种罕见的溶酶体3型疾病，具有X连锁遗传模式，由GLA基因的致病变异引起。本研究旨在描述52例墨西哥FD患者的基因型和表型。
我们纳入了在我们机构接受治疗的12例临床和分子诊断为FD的患者，以及文献中已报道的40例墨西哥FD患者。
最常见的表现为肢端感觉异常（71.2%）、少汗或无汗（48.1%）、不耐热（46.2%）和蛋白尿（42.3%）。男性的肾脏和神经表现比女性更普遍。心脏受累包括肥厚型心肌病和预激综合征心律失常。14例患者（26.9%）出现角膜涡状浑浊，15例（28.8%）出现血管角质瘤。我们在墨西哥FD患者的GLA基因中鉴定出14个变异。我们发现了一个新的变异GLA c.122C>G，它在两名无关患者中导致了一种非典型的FD表型，主要累及神经系统，其中一名患者在临床和放射学上与多发性硬化症有明显重叠，且生物标志物正常，因此需要进行肾活检以帮助确诊FD。
墨西哥FD患者的基因型和表型与其他人群相似。FD的非典型表型，如与新变异c.122C>G相关的表型，可能是一个诊断挑战，因为它可能与多发性硬化症混淆。我们的研究结果证实了非侵入性诊断方法的局限性，以及在临床高度怀疑FD时进行肾活检的必要性。
