Long-term auditory monitoring in children with Alport syndrome based on different degrees of renal injury
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摘要: 目的 探讨不同程度肾损伤的Alport综合征(alport syndrome, AS)患者远期听力变化与特点。方法 收集2007年1月至2022年9月确诊AS并完善听力学检查患者的肾脏病理、基因检测、听力检查等临床资料, 进行听力及肾功能的远期随访。结果 研究纳入AS患者70例, 随访到33例, 失访率52.9%, 随访时间1.1~15.8年, 16例患者随访时间>10年。随访患者男25例, 女8例, 随访年龄3.4~27.8岁。10例确诊AS时听力异常者随访期间均出现进行性听力下降, 随访新增听力异常者3例, 于病程5~6年时出现, 均为感音神经性耳聋, 随访13例听力下降患者中仅3例接受助听器治疗。7例发展为终末期肾病(end-stage renal disease, ESRD), 男性多见(6/7), ESRD组与非ESRD组远期听力损失率比较差异有统计学意义(P=0.013), 肾病进展变化与远期听力水平无相关(P>0.05)。28例完善肾脏活检, 均见基底膜厚薄不均及不同程度足细胞病变, 足细胞病变严重程度与远期听力损失率相关(P=0.048), 与听力损失严重程度无关(P>0.05)。11例进行基因检测, COL4A5 突变多见(8/11), 突变类型与听力表型无明显相关(P>0.05)。结论 AS患者听力可进行性下降, 远期听力进展异质性较高, 在病程5~6年时出现听力下降的概率高; 听力异常与肾病状态、肾组织病理改变及突变基因密切相关, 需要重视远期听力随访并尽早听力干预。Abstract: Objective To investigate long-term auditory changes and characteristics of Alport syndrome (AS) patients with different degrees of renal injury.Methods Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination.A long-term follow-up focusing on hearing and renal function was conducted.Results This study included 70 AS patients, of which 33(25 males, 8 females, aged 3.4-27.8 years) were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1 to 15.8 years, with 16 patients followed-up for over 10 years.During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course.All of which were sensorineural deafness.While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention.Of these patients, 7 developed end-stage renal disease (ESRD), predominantly males (6/7).The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group (P=0.013).There was no correlation between the progression of renal disease and long-term hearing level (P>0.05).kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane.The severity of podocyte lesion was correlated with the rate of long-term hearing loss (P=0.048), and there was no correlation with the severity of hearing loss (P>0.05).Among 11 cases, the COL4A5 mutationwas most common (8 out of 11), but there was no significant correlation between the mutation type and hearing phenotype (P>0.05).Conclusion AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term..THearing loss is more likely to occur 5-6 years into the disease course.Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.
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Key words:
- alport syndrome /
- children /
- long-term monitoring /
- hearing changes
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表 2 不同程度足突病变听力损失情况比较
例 听力程度 电镜足突病变 无融合 小部分融合 大部分融合 广泛融合 听力正常 0 7 7 3 轻度 0 1 0 1 中度 0 0 1 3 中重度及以上 0 1 1 3 
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表 3 不同突变基因类型听力损失情况及严重程度比较
例 听力程度 突变基因类型 COL4A3 COL4A4 COL4A5 正常 2 0 4 轻度 0 0 0 中度 1 0 3 中重度及以上 0 0 1
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表 4 两个COL4A5基因突变患者听力比较
病例 突变基因 突变位点 遗传方式 初始听力 随访听力 患者1 COL4A5 c.2060G＞A p.Gly687Glu X连锁遗传 右45/左35 中度 患者2 COL4A5 c.2060G＞A p.Gly687Glu X连锁遗传 右15/左15 正常
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