Progressive familial intrahepatic cholestasis type 3: Report of four clinical cases, novel ABCB4 variants and long-term follow-up

Introduction and objectives: Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a rare autosomal recessive cholestatic liver disorder caused by mutations in the ABCB4 gene. The aim of this study was to present the phenotypic and genotypic spectrum of 4 Polish PFIC-3 patients diagnosed...

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Autores principales:	Patryk Lipiński, Elżbieta Ciara, Dorota Jurkiewicz, Rafał Płoski, Marta Wawrzynowicz-Syczewska, Joanna Pawłowska, Irena Jankowska
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Cholestasis Progressive familial intrahepatic cholestasis Next-generation sequencing Liver transplantation Children Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/9a46db97073649f0ab4e2caea1806267
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spelling	oai:doaj.org-article:9a46db97073649f0ab4e2caea18062672021-11-18T04:46:01ZProgressive familial intrahepatic cholestasis type 3: Report of four clinical cases, novel ABCB4 variants and long-term follow-up1665-268110.1016/j.aohep.2021.100342https://doaj.org/article/9a46db97073649f0ab4e2caea18062672021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1665268121000417https://doaj.org/toc/1665-2681Introduction and objectives: Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a rare autosomal recessive cholestatic liver disorder caused by mutations in the ABCB4 gene. The aim of this study was to present the phenotypic and genotypic spectrum of 4 Polish PFIC-3 patients diagnosed in a one-referral centre. Materials and methods: The study included 4 patients with cholestasis and pathogenic variants in the ABCB4 gene identified by next-generation sequencing (NGS) of a targeted-gene panel or whole exome sequencing (WES). Clinical, laboratory, histological, and molecular data were collected. Results: Four patients (three males) were identified. The age at first noted clinical signs and symptoms was 6, 2.5, 14, and 2 years respectively; the mean age was 6 years. Those signs and symptoms include pruritus (2 out of 4 patients) and hepatomegaly with splenomegaly (4 out of 4 patients). The age at the time of referral to our centre was 9, 3, 15, and 2.5 years respectively, while the mean age was 7 years. Chronic cholestatic liver disease of unknown aetiology was established in all of them. The NGS analysis was performed in all patients at the last follow-up visit. Three novel variants including c.902T>A, p.Met301Lys, c.3279+1G>A, p.?, and c.3524T>A, p.Leu1175His were identified. The time from the first consultation to the final diagnosis was 14, 9, 3, and 1 year respectively; the mean was 6.8 years. A detailed follow-up was presented. Conclusions: The clinical phenotype of PFIC-3 could be variable. The clinical and biochemical diagnosis of PFIC-3 is difficult, thus the NGS study is very useful in making a proper diagnosis.Patryk LipińskiElżbieta CiaraDorota JurkiewiczRafał PłoskiMarta Wawrzynowicz-SyczewskaJoanna PawłowskaIrena JankowskaElsevierarticleCholestasisProgressive familial intrahepatic cholestasisNext-generation sequencingLiver transplantationChildrenSpecialties of internal medicineRC581-951ENAnnals of Hepatology, Vol 25, Iss , Pp 100342- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cholestasis Progressive familial intrahepatic cholestasis Next-generation sequencing Liver transplantation Children Specialties of internal medicine RC581-951
spellingShingle	Cholestasis Progressive familial intrahepatic cholestasis Next-generation sequencing Liver transplantation Children Specialties of internal medicine RC581-951 Patryk Lipiński Elżbieta Ciara Dorota Jurkiewicz Rafał Płoski Marta Wawrzynowicz-Syczewska Joanna Pawłowska Irena Jankowska Progressive familial intrahepatic cholestasis type 3: Report of four clinical cases, novel ABCB4 variants and long-term follow-up
description	Introduction and objectives: Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a rare autosomal recessive cholestatic liver disorder caused by mutations in the ABCB4 gene. The aim of this study was to present the phenotypic and genotypic spectrum of 4 Polish PFIC-3 patients diagnosed in a one-referral centre. Materials and methods: The study included 4 patients with cholestasis and pathogenic variants in the ABCB4 gene identified by next-generation sequencing (NGS) of a targeted-gene panel or whole exome sequencing (WES). Clinical, laboratory, histological, and molecular data were collected. Results: Four patients (three males) were identified. The age at first noted clinical signs and symptoms was 6, 2.5, 14, and 2 years respectively; the mean age was 6 years. Those signs and symptoms include pruritus (2 out of 4 patients) and hepatomegaly with splenomegaly (4 out of 4 patients). The age at the time of referral to our centre was 9, 3, 15, and 2.5 years respectively, while the mean age was 7 years. Chronic cholestatic liver disease of unknown aetiology was established in all of them. The NGS analysis was performed in all patients at the last follow-up visit. Three novel variants including c.902T>A, p.Met301Lys, c.3279+1G>A, p.?, and c.3524T>A, p.Leu1175His were identified. The time from the first consultation to the final diagnosis was 14, 9, 3, and 1 year respectively; the mean was 6.8 years. A detailed follow-up was presented. Conclusions: The clinical phenotype of PFIC-3 could be variable. The clinical and biochemical diagnosis of PFIC-3 is difficult, thus the NGS study is very useful in making a proper diagnosis.
format	article
author	Patryk Lipiński Elżbieta Ciara Dorota Jurkiewicz Rafał Płoski Marta Wawrzynowicz-Syczewska Joanna Pawłowska Irena Jankowska
author_facet	Patryk Lipiński Elżbieta Ciara Dorota Jurkiewicz Rafał Płoski Marta Wawrzynowicz-Syczewska Joanna Pawłowska Irena Jankowska
author_sort	Patryk Lipiński
title	Progressive familial intrahepatic cholestasis type 3: Report of four clinical cases, novel ABCB4 variants and long-term follow-up
title_short	Progressive familial intrahepatic cholestasis type 3: Report of four clinical cases, novel ABCB4 variants and long-term follow-up
title_full	Progressive familial intrahepatic cholestasis type 3: Report of four clinical cases, novel ABCB4 variants and long-term follow-up
title_fullStr	Progressive familial intrahepatic cholestasis type 3: Report of four clinical cases, novel ABCB4 variants and long-term follow-up
title_full_unstemmed	Progressive familial intrahepatic cholestasis type 3: Report of four clinical cases, novel ABCB4 variants and long-term follow-up
title_sort	progressive familial intrahepatic cholestasis type 3: report of four clinical cases, novel abcb4 variants and long-term follow-up
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/9a46db97073649f0ab4e2caea1806267
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Progressive familial intrahepatic cholestasis type 3: Report of four clinical cases, novel ABCB4 variants and long-term follow-up

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