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肾脏病与透析肾移植杂志 ›› 2026, Vol. 35 ›› Issue (5): 434-439.DOI: 10.3969/j.issn.1006-298X.2026.05.006

• 论著 • 上一篇    下一篇

糖原贮积病肾损害的基因突变与临床病理分析

  

  • 出版日期:2026-10-27 发布日期:2026-10-27

Genetic and clinicopathological characteristics of renal impairment in glycogen storage disease

  • Online:2026-10-27 Published:2026-10-27

摘要:

目的:探讨成人糖原贮积病(glycogen storage disease,GSD)相关肾损害的临床病理特点、遗传学特征及诊疗策略。方法:回顾性分析2000年6月至2025年7月在国家肾脏疾病临床医学研究中心确诊的5例成人GSD肾损害患者的临床资料、肾脏病理及基因突变特征。结果:5例患者(GSD Ia型4例,GSD Ib型1例)均存在典型代谢紊乱及蛋白尿。肾脏病理特征为光镜下肾小管上皮细胞核内空泡变性、PAS染色强阳性;电镜下肾小管上皮细胞核内可见糖原颗粒沉积(直径14~32 nm)。基因检测证实常染色体隐性遗传模式,3例GSD Ia型患者为G6PC1基因纯合突变(c.648G>T或c.964T>G),父母双方均携带相应的杂合变异。1例GSD Ib型患者为SLC37A4基因复合杂合突变,c.870+5G>A(来自父亲)和c.775_776delinsA(来自母亲),其中c.775_776delinsA为新突变。中位随访9个月,4例患者肾功能稳定,1例于确诊后15个月死于上消化道出血。结论:成人GSD患者兼具代谢紊乱和肾损害,电镜下肾小管上皮细胞核内糖原颗粒沉积是重要诊断指标。

Abstract:

Objective: To investigate the clinicopathological characteristics, genetic features, and diagnosis and treatment strategies of renal impairment associated with adult glycogen storage disease (GSD). Methods: The clinical data, renal pathological features, and genetic mutations of 5 adult patients with confirmed GSD-related renal impairment were retrospectively analyzed. Results: All 5 patients (4 patients with GSD type Ia and 1 with GSD type Ib) presented with characteristic metabolic disorders and proteinuria. Key renal pathological manifestations included vacuolar degeneration in the nuclei of renal tubular epithelial cells (strongly positive for periodic acid-schiff), and deposition of glycogen particles (14-32 nm in diameter) in the nuclei of renal tubular epithelial cells on electron microscopy. Genetic testing confirmed an autosomal recessive inheritance pattern. Three patients with GSD type Ia carried homozygous mutations in the G6PC1 gene (c.648G>T or c.964T>G), with both parents carrying the same heterozygous mutations. One patient with GSD type Ib exhibited compound heterozygous mutations in the SLC37A4 gene: c.870+5G>A (paternal) and c.775_776delinsA (maternal), among which c.775_776delinsA was a novel mutation. During a median follow-up of 9 months, renal function remained stable in 4 patients, while 1 patient died of upper gastrointestinal bleeding 15 months after diagnosis. Conclusion: Adult patients with GSD frequently exhibit both metabolic disorders and renal impairment. The deposition of glycogen particles in the nuclei of renal tubular epithelial cells on electron microscopy serves as a key diagnostic marker.

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