Fuller Maria, Perry Rebecca, Saiedi Madiha, Fletcher Janice M, Selvanayagam Joseph B
Genetics and Molecular Pathology, SA Pathology at Women's and Children's Hospital, 72 King William Road, North Adelaide, South Australia 5006, Australia.
Adelaide Medical School, University of Adelaide, Adelaide, South Australia 5005, Australia.
Mol Genet Metab Rep. 2020 Dec 10;25:100697. doi: 10.1016/j.ymgmr.2020.100697. eCollection 2020 Dec.
Fabry disease (FD) results from a deficiency in the exoglycohydrolase, α-galactosidase A (AGA), an enzyme required for the sequential degradation of glycosphingolipids, which consequently accumulate in the lysosomes of affected cells. An X-linked inherited metabolic disorder, FD has a high incidence of a later onset phenotype that is under-diagnosed and under-recognised in adulthood despite the availability of specific treatment. As the first presenting feature in adults is often left ventricular hypertrophy (LVH), we hypothesized that testing patients with an attenuated echocardiographic phenotype of unexplained hypertrophic cardiomyopathy, might identify cases of undiagnosed FD. We employed a simple screening test by measuring AGA activity in dried blood spots collected from a finger-prick of blood in a cohort of 511 individuals aged between 18 and 75 with LVH between 1.2 and 1.5 cm. Two males were identified with AGA activity below the reference interval and subsequent molecular testing confirmed the commonly reported genetic variants, p.Ala143Thr in one individual and p.Asn215Ser, in the other. Additional biochemical measurement of plasma, lyso-Gb1 was normal in both patients. Of the 179 females screened, one individual returned AGA activity slightly below the reference interval but was lost to further follow-up. This pilot study suggests that screening patients with mild-to-moderate LVH of unknown aetiology does indeed identify undiagnosed cases of FD.
法布里病（FD）是由于外切糖苷酶α-半乳糖苷酶A（AGA）缺乏所致，AGA是糖鞘脂顺序降解所需的一种酶，糖鞘脂因此在受影响细胞的溶酶体中蓄积。FD是一种X连锁遗传性代谢紊乱疾病，其迟发型表型发病率高，尽管有特效治疗方法，但在成年期仍未得到充分诊断和认识。由于成年人的首发症状通常是左心室肥厚（LVH），我们推测，对具有无法解释的肥厚型心肌病超声心动图衰减表型的患者进行检测，可能会发现未诊断的FD病例。我们采用了一种简单的筛查试验，通过测量从511名年龄在18至75岁、左心室肥厚程度在1.2至1.5厘米之间的个体手指采血获得的干血斑中的AGA活性。两名男性被确定其AGA活性低于参考区间，随后的分子检测证实了常见的基因变异，一名个体为p.Ala143Thr，另一名个体为p.Asn215Ser。两名患者血浆溶血型Gb1的其他生化检测结果均正常。在接受筛查的179名女性中，有一名个体的AGA活性略低于参考区间，但失访未能进一步跟进。这项初步研究表明，对病因不明的轻至中度LVH患者进行筛查确实可以发现未诊断的FD病例。
