Differences in presentation and progression between severe FIC1 and BSEP deficiencies

Ludmila Pawlikowska; Sandra Strautnieks; Irena Jankowska; Piotr Czubkowski; Karan Emerick; Anthony Antoniou; Catherine Wanty; Bjorn Fischler; Emmanuel Jacquemin; Sami Wali; Samra Blanchard; Inge Merete Nielsen; Billy Bourke; Shirley McQuaid; Florence Lacaille; Jane A. Byrne; Albertien M. van Eerde; Kaija Leena Kolho; Leo Klomp; Roderick Houwen; Peter Bacchetti; Steven Lobritto; Vera Hupertz; Patricia McClean; Giorgina Mieli-Vergani; Benjamin Shneider; Antal Nemeth; Etienne Sokal; Nelson B. Freimer; A. S. Knisely; Philip Rosenthal; Peter F. Whitington; Joanna Pawlowska; Richard J. Thompson; Laura N. Bull

doi:10.1016/j.jhep.2010.01.034

Differences in presentation and progression between severe FIC1 and BSEP deficiencies

Ludmila Pawlikowska, Sandra Strautnieks, Irena Jankowska, Piotr Czubkowski, Karan Emerick, Anthony Antoniou, Catherine Wanty, Bjorn Fischler, Emmanuel Jacquemin, Sami Wali, Samra Blanchard, Inge Merete Nielsen, Billy Bourke, Shirley McQuaid, Florence Lacaille, Jane A. Byrne, Albertien M. van Eerde, Kaija Leena Kolho, Leo Klomp, Roderick HouwenPeter Bacchetti, Steven Lobritto, Vera Hupertz, Patricia McClean, Giorgina Mieli-Vergani, Benjamin Shneider, Antal Nemeth, Etienne Sokal, Nelson B. Freimer, A. S. Knisely, Philip Rosenthal, Peter F. Whitington, Joanna Pawlowska, Richard J. Thompson, Laura N. Bull^*

^*Corresponding author for this work

Medical Genetics Program

116 Citations (Scopus)

Abstract

Background & Aims: 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.

Original language	English
Journal	Journal of Hepatology
Volume	53
Issue number	1
Pages (from-to)	170-178
Number of pages	9
ISSN	0168-8278
DOIs	https://doi.org/10.1016/j.jhep.2010.01.034
Publication status	Published - 1 Jul 2010

Keywords

ABCB11
ATP binding cassette protein
ATP8B1
BSEP
Cholestasis
FIC1
Genetics
P-type ATPase
Pediatrics
Transport protein

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jhep.2010.01.034

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Pawlikowska, L., Strautnieks, S., Jankowska, I., Czubkowski, P., Emerick, K., Antoniou, A., Wanty, C., Fischler, B., Jacquemin, E., Wali, S., Blanchard, S., Nielsen, I. M., Bourke, B., McQuaid, S., Lacaille, F., Byrne, J. A., van Eerde, A. M., Kolho, K. L., Klomp, L., ... Bull, L. N. (2010). Differences in presentation and progression between severe FIC1 and BSEP deficiencies. Journal of Hepatology, 53(1), 170-178. https://doi.org/10.1016/j.jhep.2010.01.034

Pawlikowska, L, Strautnieks, S, Jankowska, I, Czubkowski, P, Emerick, K, Antoniou, A, Wanty, C, Fischler, B, Jacquemin, E, Wali, S, Blanchard, S, Nielsen, IM, Bourke, B, McQuaid, S, Lacaille, F, Byrne, JA, van Eerde, AM, Kolho, KL, Klomp, L, Houwen, R, Bacchetti, P, Lobritto, S, Hupertz, V, McClean, P, Mieli-Vergani, G, Shneider, B, Nemeth, A, Sokal, E, Freimer, NB, Knisely, AS, Rosenthal, P, Whitington, PF, Pawlowska, J, Thompson, RJ & Bull, LN 2010, 'Differences in presentation and progression between severe FIC1 and BSEP deficiencies', Journal of Hepatology, vol. 53, no. 1, pp. 170-178. https://doi.org/10.1016/j.jhep.2010.01.034

@article{e2a7fe72c1924351ba821a9fd8dc56d4,

title = "Differences in presentation and progression between severe FIC1 and BSEP deficiencies",

abstract = "Background & Aims: 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.",

keywords = "ABCB11, ATP binding cassette protein, ATP8B1, BSEP, Cholestasis, FIC1, Genetics, P-type ATPase, Pediatrics, Transport protein",

author = "Ludmila Pawlikowska and Sandra Strautnieks and Irena Jankowska and Piotr Czubkowski and Karan Emerick and Anthony Antoniou and Catherine Wanty and Bjorn Fischler and Emmanuel Jacquemin and Sami Wali and Samra Blanchard and Nielsen, {Inge Merete} and Billy Bourke and Shirley McQuaid and Florence Lacaille and Byrne, {Jane A.} and {van Eerde}, {Albertien M.} and Kolho, {Kaija Leena} and Leo Klomp and Roderick Houwen and Peter Bacchetti and Steven Lobritto and Vera Hupertz and Patricia McClean and Giorgina Mieli-Vergani and Benjamin Shneider and Antal Nemeth and Etienne Sokal and Freimer, {Nelson B.} and Knisely, {A. S.} and Philip Rosenthal and Whitington, {Peter F.} and Joanna Pawlowska and Thompson, {Richard J.} and Bull, {Laura N.}",

year = "2010",

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day = "1",

doi = "10.1016/j.jhep.2010.01.034",

language = "English",

volume = "53",

pages = "170--178",

journal = "Journal of Hepatology, Supplement",

issn = "0169-5185",

publisher = "Elsevier",

number = "1",

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TY - JOUR

T1 - Differences in presentation and progression between severe FIC1 and BSEP deficiencies

AU - Pawlikowska, Ludmila

AU - Strautnieks, Sandra

AU - Jankowska, Irena

AU - Czubkowski, Piotr

AU - Emerick, Karan

AU - Antoniou, Anthony

AU - Wanty, Catherine

AU - Fischler, Bjorn

AU - Jacquemin, Emmanuel

AU - Wali, Sami

AU - Blanchard, Samra

AU - Nielsen, Inge Merete

AU - Bourke, Billy

AU - McQuaid, Shirley

AU - Lacaille, Florence

AU - Byrne, Jane A.

AU - van Eerde, Albertien M.

AU - Kolho, Kaija Leena

AU - Klomp, Leo

AU - Houwen, Roderick

AU - Bacchetti, Peter

AU - Lobritto, Steven

AU - Hupertz, Vera

AU - McClean, Patricia

AU - Mieli-Vergani, Giorgina

AU - Shneider, Benjamin

AU - Nemeth, Antal

AU - Sokal, Etienne

AU - Freimer, Nelson B.

AU - Knisely, A. S.

AU - Rosenthal, Philip

AU - Whitington, Peter F.

AU - Pawlowska, Joanna

AU - Thompson, Richard J.

AU - Bull, Laura N.

PY - 2010/7/1

Y1 - 2010/7/1

N2 - Background & Aims: 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.

AB - Background & Aims: 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.

KW - ABCB11

KW - ATP binding cassette protein

KW - ATP8B1

KW - BSEP

KW - Cholestasis

KW - FIC1

KW - Genetics

KW - P-type ATPase

KW - Pediatrics

KW - Transport protein

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U2 - 10.1016/j.jhep.2010.01.034

DO - 10.1016/j.jhep.2010.01.034

M3 - Journal article

C2 - 20447715

AN - SCOPUS:77953587817

SN - 0169-5185

VL - 53

SP - 170

EP - 178

JO - Journal of Hepatology, Supplement

JF - Journal of Hepatology, Supplement

IS - 1

ER -

Differences in presentation and progression between severe FIC1 and BSEP deficiencies

Abstract

Keywords

UN SDGs

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