Although Fanconi syndrome (FS) induced by valproate (VPA) has occasionally been reported, the detailed clinical features of the disease remain unclear. The aim of this study was to elucidate the clinical features of patients with VPA-induced FS.

We searched Chinese and English databases for all original studies, clinical reports, and case reports on VPA-induced FS published before March 2022.

A total of 29 articles including 54 patients (28 males and 24 females) were included. The patients had a median age of 7 years (range 2–34 years), had severely disabled (87.0%), tube feeding (64.8%), and received an average of 1.8 medications other than VPA. The median duration of VPA treatment was 4 years (range 0.7–15.5). Pathological fractures (25.9%), unexplained fever (11.1%), muscle weakness (9.3%), and edema (9.3%) were the most common symptoms, while 18 patients were diagnosed in incidental laboratory tests. Blood tests revealed hypokalemia (69.2%), hypophosphatemia (98.0%), and hypouricemia (93.3%). Urinalysis revealed glucosuria (96.1%), proteinuria (100.0%), generalized hyperaminoaciduria (100.0 %), β2 macroglobulin (100.0%). Decreased percent total reabsorption of phosphate (%TRP) found in 94.1% of patients, and increased fractional excretion of uric acid (FEUA) were found in 100% of patients. The median time to resolution of FS after discontinuation of drug therapy was 3 months (range 0.25–18).

The possibility of FS needs to be considered with long-term VPA administration, especially in young, tube-fed, severely disabled patients who are co-administered with anticonvulsants. Patients receiving VPA should have regular blood and urine tests. Abnormal laboratory values returned to normal levels after VPA discontinuation.

尽管偶有报道由丙戊酸盐 (VPA) 引起的范可尼综合征 (FS)，但该疾病的详细临床特征仍不清楚。本研究的目的是阐明 VPA 诱导的 FS 患者的临床特征。

我们检索了中文和英文数据库中所有在 2022 年 3 月之前发表的关于 VPA 诱导的 FS 的原始研究、临床报告和病例报告。

共纳入29篇文章，包括54名患者（28名男性和24名女性）。患者的中位年龄为 7 岁（范围 2-34 岁），严重残疾（87.0%），管饲（64.8%），平均接受了 1.8 种除 VPA 以外的药物。VPA 治疗的中位持续时间为 4 年（范围 0.7-15.5）。病理性骨折（25.9%）、不明原因发热（11.1%）、肌肉无力（9.3%）和水肿（9.3%）是最常见的症状，而18名患者在偶然的实验室检查中被确诊。血液检查显示低钾血症（69.2%）、低磷血症（98.0%）和低尿酸血症（93.3%）。尿液分析显示糖尿（96.1%）、蛋白尿（100.0%）、全身性高氨基酸尿（100.0%）、β2巨球蛋白（100.0%）。在 94.1% 的患者中发现磷酸盐的总重吸收百分比 (%TRP) 降低，在 100% 的患者中发现尿酸排泄分数 (FEUA) 增加。停止药物治疗后 FS 消退的中位时间为 3 个月（范围 0.25-18）。

长期服用 VPA 时需要考虑 FS 的可能性，尤其是在年轻、管饲、严重残疾的患者中，同时服用抗惊厥药。接受 VPA 的患者应定期进行血液和尿液检查。停用 VPA 后，异常实验室值恢复到正常水平。