Biallelic variants in the USP53 gene have recently been reported to segregate with normal gamma glutamyltransferase (GGT) cholestasis. Using whole-exome sequencing (WES), we detected two USP53 homozygous variants (c.951delT; p. Phe317fs and c.1744C>T; p. Arg582*) in five additional cases, including an unpublished cousin of a previously described family with intractable itching and normal GGT cholestasis. Three patients, a child and two adults, presented with recurrent episodes of normal GGT cholestasis, consistent with a diagnosis of benign recurrent intrahepatic cholestasis (BRIC). Cholangiopathic changes, possibly autoimmune in origin, were recognized in some patients. Additional phenotypic details in one patient included an enlarged left kidney, and speech/developmental delay. Notably, two patients exhibited a complete response to rifampicin, and one responded to ursodeoxycholic acid (UDCA). Two adult patients were suspected to have autoimmune liver disease and treated with steroids. This report describes new cases of USP53 disease presenting with normal GGT cholestasis or BRIC in three children and two adults. We also describe the novel finding of a dramatic response to rifampicin. The association of cholangiopathy with normal GGT cholestasis provides a diagnostic challenge and remains poorly understood.

USP53基因的双等位基因变体最近有报道与正常的γ-谷氨酰转移酶（GGT）胆汁淤积症分离。使用全外显子测序（WES），我们检测到两个 USP53纯合子变体（c.951delT； p.Phe317fs和c.1744C> T； p.Arg582 *）在另外五种情况下，包括先前描述的家族的未发表表亲，具有顽固的瘙痒和正常的GGT胆汁淤积。三名患者，一个孩子和两个成年人，表现为正常GGT胆汁淤积的复发发作，与良性复发性肝内胆汁淤积（BRIC）的诊断一致。在某些患者中发现了胆源性改变，可能是自身免疫性起源。一名患者的其他表型细节包括左肾增大，以及言语/发育迟缓。值得注意的是，两名患者对利福平表现出完全缓解，一名对熊去氧胆酸（UDCA）发生了反应。两名成年患者被怀疑患有自身免疫性肝病，并接受类固醇治疗。该报告描述了在3名儿童和2名成人中出现正常GGT胆汁淤积或BRIC的USP53疾病新病例。我们还描述了对利福平产生戏剧性反应的新颖发现。胆管疾病与正常GGT胆汁淤积的相关性提供了诊断挑战，并且仍知之甚少。