Lykavieris Panayotis, van Mil Saskia, Cresteil Danièle, Fabre Monique, Hadchouel Michelle, Klomp Leo, Bernard Olivier, Jacquemin Emmanuel
Department of Pediatrics, Hepatology Unit, Bicêtre University Hospital, Assistance Publique--Hôpitaux de Paris, 78, rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France.
J Hepatol. 2003 Sep;39(3):447-52. doi: 10.1016/s0168-8278(03)00286-1.
BACKGROUND/AIMS: Progressive familial intrahepatic cholestasis characterized by normal serum gamma-glutamyltransferase activity can be due to mutations in familial intrahepatic cholestasis type 1 (FIC1) (ATP8B1), a gene expressed in several organs. In some cases, it is associated with extrahepatic features. We searched for FIC1 mutations and analyzed the outcome of extrahepatic features after liver transplantation in two children with this form of progressive familial intrahepatic cholestasis associated with chronic unexplained diarrhea and short stature.
FIC1 sequence was determined after polymerase chain reaction (PCR) of genomic lymphocyte DNA and/or reverse transcription-PCR of liver or lymphocyte RNA.
A homozygous amino acid change deletion was found in one child. The second child harboured compound heterozygous missense and nonsense mutations. In both children, despite successful liver transplantation, evolution (follow-up: 9.5-11 years) was characterized by exacerbation of diarrhea and no catch-up of stature growth, and appearance of liver steatosis.
Progressive familial intrahepatic cholestasis characterized by normal serum gamma-glutamyltransferase activity and extrahepatic features corresponds to progressive familial intrahepatic cholestasis type 1. Extrahepatic symptomatology is not corrected or may be aggravated by liver transplantation, impairing life quality.
背景/目的：以血清γ-谷氨酰转移酶活性正常为特征的进行性家族性肝内胆汁淤积可能是由于家族性肝内胆汁淤积1型（FIC1）（ATP8B1）基因突变所致，该基因在多个器官中表达。在某些情况下，它与肝外表现相关。我们在两名患有这种与慢性不明原因腹泻和身材矮小相关的进行性家族性肝内胆汁淤积的儿童中寻找FIC1突变，并分析肝移植后肝外表现的结局。
通过对基因组淋巴细胞DNA进行聚合酶链反应（PCR）和/或对肝脏或淋巴细胞RNA进行逆转录PCR来确定FIC1序列。
在一名儿童中发现了纯合氨基酸改变缺失。第二名儿童携带复合杂合错义突变和无义突变。在这两名儿童中，尽管肝移植成功，但随访9.5至11年的病情发展表现为腹泻加重、身材未追赶生长以及出现肝脂肪变性。
以血清γ-谷氨酰转移酶活性正常和肝外表现为特征的进行性家族性肝内胆汁淤积对应于进行性家族性肝内胆汁淤积1型。肝外症状不能通过肝移植得到纠正，甚至可能加重，从而影响生活质量。
