Department of Medicine, Division of Nephrology, Kurume University School of Medicine, Fukuoka, Japan.
Department of Functional Bioanalysis, Meiji Pharmaceutical University, Tokyo, Japan.
Nephrol Dial Transplant. 2021 Dec 31;37(1):115-125. doi: 10.1093/ndt/gfaa324.
Fabry disease (FD), an X-linked lysosomal storage disorder caused by a deficiency in alfa-galactosidase A (α-Gal A) activity due to mutations in the GLA gene, has a prevalence of 0-1.69% in patients undergoing haemodialysis; however, its prevalence in patients with chronic kidney disease (CKD) Stages 1-5 is unknown.
Serum α-Gal A activity analysis and direct sequencing of GLA were used to screen for FD in 2122 male patients with CKD, including 1703 patients with CKD Stage 5D and 419 with CKD Stages 1-5. The correlation between serum α-Gal A activity and confounding factors in patients with CKD Stages 1-5 was evaluated.
FD prevalence rates in patients with CKD Stage 5D and CKD Stages 1-5 were 0.06% (1/1703) and 0.48% (2/419), respectively. A patient with CKD Stage 5D exhibited a novel GLA mutation, p.Met208Arg, whereas two patients with CKD Stages 1-5 had c.370delG and p.Met296Ile. p. Met208Arg caused moderate structural changes in the molecular surface region near the substituted amino acid residue but did not affect the catalytic residues Asp170 and Asp231 in α-Gal A. Serum α-Gal A activity in patients with CKD Stages 1-5 was inversely correlated with age (P < 0.0001) but directly correlated with estimated glomerular filtration rate (P < 0.0001).
FD prevalence was much higher in male patients with CKD Stages 1-5 than in those with CKD Stage 5D. FD screening in patients with CKD Stages 1-5 may improve patient survival, decreasing the number of patients with CKD Stage 5D.
法布里病（FD）是一种 X 连锁溶酶体贮积症，由于 GLA 基因的突变导致α-半乳糖苷酶 A（α-Gal A）活性缺乏，其患病率在接受血液透析的患者中为 0-1.69%；然而，其在慢性肾脏病（CKD）1-5 期患者中的患病率尚不清楚。
对 2122 例男性 CKD 患者（包括 1703 例 CKD 5D 患者和 419 例 CKD 1-5 期患者）进行血清α-Gal A 活性分析和 GLA 直接测序，以筛查 FD。评估 CKD 1-5 期患者血清α-Gal A 活性与混杂因素的相关性。
CKD 5D 患者和 CKD 1-5 期患者的 FD 患病率分别为 0.06%（1/1703）和 0.48%（2/419）。一名 CKD 5D 患者存在新的 GLA 突变 p.Met208Arg，而两名 CKD 1-5 期患者分别存在 c.370delG 和 p.Met296Ile。p.Met208Arg 导致分子表面区域靠近取代氨基酸残基的结构发生中度改变，但不影响α-Gal A 中的催化残基 Asp170 和 Asp231。CKD 1-5 期患者的血清α-Gal A 活性与年龄呈负相关（P<0.0001），与估计肾小球滤过率呈正相关（P<0.0001）。
CKD 1-5 期男性患者 FD 的患病率明显高于 CKD 5D 患者。对 CKD 1-5 期患者进行 FD 筛查可能会改善患者的生存状况，降低 CKD 5D 患者的数量。
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