title: Differences in presentation and progression between severe FIC1 and BSEP deficiencies.
abstract: OBJECTIVE
  Progressive familial intrahepatic cholestasis (PFIC) with normal serum levels of gamma-glutamyltranspeptidase can result from mutations in ATP8B1 (encoding familial intrahepatic cholestasis 1 [FIC1]) or ABCB11 (encoding bile salt export pump [BSEP]). We evaluated clinical and laboratory features of disease in patients diagnosed with PFIC, who carried mutations in ATP8B1 (FIC1 deficiency) or ABCB11 (BSEP deficiency). Our goal was to identify features that distinguish presentation and course of these two disorders, thus facilitating diagnosis and elucidating the differing consequences of ATP8B1 and ABCB11 mutations.
  
  
  METHODS
  A retrospective multi-center study was conducted, using questionnaires and chart review. Available clinical and biochemical data from 145 PFIC patients with mutations in either ATP8B1 (61 "FIC1 patients") or ABCB11 (84 "BSEP patients") were evaluated.
  
  
  RESULTS
  At presentation, serum aminotransferase and bile salt levels were higher in BSEP patients; serum alkaline phosphatase values were higher, and serum albumin values were lower, in FIC1 patients. Elevated white blood cell counts, and giant or multinucleate cells at liver biopsy, were more common in BSEP patients. BSEP patients more often had gallstones and portal hypertension. Diarrhea, pancreatic disease, rickets, pneumonia, abnormal sweat tests, hearing impairment, and poor growth were more common in FIC1 patients. Among BSEP patients, the course of disease was less rapidly progressive in patients bearing the D482G mutation.
  
  
  CONCLUSIONS
  Severe forms of FIC1 and BSEP deficiency differed. BSEP patients manifested more severe hepatobiliary disease, while FIC1 patients showed greater evidence of extrahepatic disease.
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Pawlikowska
authors.forename: Sandra
authors.initials: S
authors.lastname: Strautnieks
authors.forename: Irena
authors.initials: I
authors.lastname: Jankowska
authors.forename: Piotr
authors.initials: P
authors.lastname: Czubkowski
authors.forename: Karan
authors.initials: K
authors.lastname: Emerick
authors.forename: Anthony
authors.initials: A
authors.lastname: Antoniou
authors.forename: Catherine
authors.initials: C
authors.lastname: Wanty
authors.forename: Bjorn
authors.initials: B
authors.lastname: Fischler
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Jacquemin
authors.forename: Sami
authors.initials: S
authors.lastname: Wali
authors.forename: Samra
authors.initials: S
authors.lastname: Blanchard
authors.forename: Inge-Merete
authors.initials: IM
authors.lastname: Nielsen
authors.forename: Billy
authors.initials: B
authors.lastname: Bourke
authors.forename: Shirley
authors.initials: S
authors.lastname: McQuaid
authors.forename: Florence
authors.initials: F
authors.lastname: Lacaille
authors.forename: Jane A
authors.initials: JA
authors.lastname: Byrne
authors.forename: Albertien M
authors.initials: AM
authors.lastname: van Eerde
authors.forename: Kaija-Leena
authors.initials: KL
authors.lastname: Kolho
authors.forename: Leo
authors.initials: L
authors.lastname: Klomp
authors.forename: Roderick
authors.initials: R
authors.lastname: Houwen
authors.forename: Peter
authors.initials: P
authors.lastname: Bacchetti
authors.forename: Steven
authors.initials: S
authors.lastname: Lobritto
authors.forename: Vera
authors.initials: V
authors.lastname: Hupertz
authors.forename: Patricia
authors.initials: P
authors.lastname: McClean
authors.forename: Giorgina
authors.initials: G
authors.lastname: Mieli-Vergani
authors.forename: Benjamin
authors.initials: B
authors.lastname: Shneider
authors.forename: Antal
authors.initials: A
authors.lastname: Nemeth
authors.forename: Etienne
authors.initials: E
authors.lastname: Sokal
authors.forename: Nelson B
authors.initials: NB
authors.lastname: Freimer
authors.forename: A S
authors.initials: AS
authors.lastname: Knisely
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenthal
authors.forename: Peter F
authors.initials: PF
authors.lastname: Whitington
authors.forename: Joanna
authors.initials: J
authors.lastname: Pawlowska
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Thompson
authors.forename: Laura N
authors.initials: LN
authors.lastname: Bull
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000172:deficiency* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001647:Bile Acids and Salts / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D012189:Retrospective Studies; D055815:Young Adult; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D005723:gamma-Glutamyltransferase; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human
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