Kuloglu Zarife, Balcı Deniz, Haskoloğlu Zehra Şule, Kendirli Tanıl, Bingöl-Koloğlu Meltem, Tuna-Kırsaçlıoğlu Ceyda, Bal Sevgi, Selbuz Suna, Kırımker Onur, Savaş Berna, Altuntaş Cansu, Güner Şükrü Nail, Can Özlem Selvi, Karayalçın Kaan, Doğu Figen, Kansu Tanca Aydan, İkincioğulları Aydan
Division of Pediatric Gastroenterology, Hepatology and Nutrition, Ankara University School of Medicine, Ankara, Turkey.
Deparment of General Surgery, Ankara University School of Medicine, Ankara, Turkey.
Pediatr Transplant. 2019 Nov;23(7):e13545. doi: 10.1111/petr.13545. Epub 2019 Jul 11.
DOCK8 deficiency is a rare inherited combined immunodeficiency, caused by mutations in the DOCK8 gene. We describe a case with DOCK8 deficiency associated with severe CLD in whom orthotopic LT was performed successfully after allogeneic HSCT. A 5 year-old girl with DOCK8 deficiency presented with mild direct hyperbilirubinemia and abnormal GGT level and without a previous history of jaundice. She had severe growth retardation, hepatosplenomegaly and generalized eczema. Progressive worsening of CLD was observed within 4 months. Investigations for etiology of liver disease were negative. Liver biopsy showed bridging necrosis, cholestasis and, cirrhosis. Recurrent immune hemolytic crisis and several viral infections developed in follow-up. She underwent whole cadaveric LT for end-stage liver disease (ESLD) 1 year after allogenic HSCT from a full matched related donor. The postoperative course was uneventful. The patient is alive with normal liver function and moderate skin graft versus host disease for 36 months after LT. In conclusion DOCK8 deficiency can be associated with severe CLD. Successful LT following HSCT is possible in patients with ESLD in DOCK8 deficiency. The timing of LT is challenging in patients requiring both HSCT and LT since conditioning regimens for HSCT can be highly hepatotoxic and the patients with suboptimal liver function can become decompensated during HSCT.
DOCK8缺陷是一种由DOCK8基因突变引起的罕见遗传性联合免疫缺陷病。我们描述了一例DOCK8缺陷合并严重慢性肝病（CLD）的病例，该患者在异基因造血干细胞移植（HSCT）后成功接受了原位肝移植（LT）。一名患有DOCK8缺陷的5岁女孩出现轻度直接胆红素血症和谷氨酰转肽酶（GGT）水平异常，既往无黄疸病史。她有严重的生长发育迟缓、肝脾肿大和全身性湿疹。在4个月内观察到CLD逐渐恶化。对肝病病因的检查均为阴性。肝活检显示桥接坏死、胆汁淤积和肝硬化。随访中出现复发性免疫溶血危机和几次病毒感染。在接受来自全相合相关供体的异基因HSCT 1年后，她因终末期肝病（ESLD）接受了全尸体LT。术后过程顺利。肝移植后36个月，患者存活，肝功能正常，有中度皮肤移植物抗宿主病。总之，DOCK8缺陷可能与严重CLD相关。对于DOCK8缺陷合并ESLD的患者，HSCT后成功进行肝移植是可能的。对于需要同时进行HSCT和LT的患者，肝移植的时机具有挑战性，因为HSCT的预处理方案可能具有高度肝毒性，肝功能欠佳的患者在HSCT期间可能会发生失代偿。
