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Cholestasis, progressive familial intrahepatic, 4(PFIC4)

MedGen UID:
418976
Concept ID:
C2931067
Disease or Syndrome
Synonyms: Cholestasis, progressive familial intrahepatic 4; PFIC4 Progressive familial intrahepatic cholestasis type 4; Progressive familial intrahepatic cholestasis 4
SNOMED CT: PFIC4 - progressive familial intrahepatic cholestasis type 4 (1295517006); Progressive familial intrahepatic cholestasis type 4 (1295517006); Progressive familial intrahepatic cholestasis type IV (1295517006); TJP2 deficit (1295517006)
 
Gene (location): TJP2 (9q21.11)
 
Monarch Initiative: MONDO:0014381
OMIM®: 615878
Orphanet: ORPHA480483

Definition

Disease with characteristics of early childhood onset of severe progressive liver disease. Caused by homozygous or compound heterozygous mutation in the TJP2 gene on chromosome 9q21. [from SNOMEDCT_US]

Clinical features

From HPO
Portal hypertension
MedGen UID:
9375
Concept ID:
C0020541
Disease or Syndrome
Increased pressure in the portal vein.
Intrahepatic cholestasis
MedGen UID:
3042
Concept ID:
C0008372
Disease or Syndrome
Impairment of bile flow due to obstruction in the small bile ducts within the liver.
Cirrhosis of liver
MedGen UID:
7368
Concept ID:
C0023890
Disease or Syndrome
A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function.
Liver failure
MedGen UID:
88444
Concept ID:
C0085605
Disease or Syndrome
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.
Hepatocellular carcinoma
MedGen UID:
389187
Concept ID:
C2239176
Neoplastic Process
Hepatocellular carcinoma is the major histologic type of malignant primary liver neoplasm. It is the fifth most common cancer and the third most common cause of death from cancer worldwide. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. Hepatoblastomas comprise 1 to 2% of all malignant neoplasms of childhood, most often occurring in children under 3 years of age. Hepatoblastomas are thought to be derived from undifferentiated hepatocytes (Taniguchi et al., 2002).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCholestasis, progressive familial intrahepatic, 4

Professional guidelines

PubMed

Feldman AG, Sokol RJ
Semin Pediatr Surg 2020 Aug;29(4):150945. Epub 2020 Jul 23 doi: 10.1016/j.sempedsurg.2020.150945. PMID: 32861449Free PMC Article
Gonzales E, Spraul A, Jacquemin E
Eur J Hum Genet 2014 Apr;22(4) Epub 2013 Sep 4 doi: 10.1038/ejhg.2013.188. PMID: 24002166Free PMC Article
Gonzales E, Spraul A, Jacquemin E
Eur J Hum Genet 2014 Apr;22(4) Epub 2013 Aug 28 doi: 10.1038/ejhg.2013.186. PMID: 23982690Free PMC Article

Recent clinical studies

Etiology

Miethke AG, Moukarzel A, Porta G, Covarrubias Esquer J, Czubkowski P, Ordonez F, Mosca A, Aqul AA, Squires RH, Sokal E, D'Agostino D, Baumann U, D'Antiga L, Kasi N, Laborde N, Arikan C, Lin CH, Gilmour S, Mittal N, Chiou FK, Horslen SP, Huber WD, Jaecklin T, Nunes T, Lascau A, Longpre L, Mogul DB, Garner W, Vig P, Hupertz VF, Gonzalez-Peralta RP, Ekong U, Hartley J, Laverdure N, Ovchinsky N, Thompson RJ
Lancet Gastroenterol Hepatol 2024 Jul;9(7):620-631. Epub 2024 May 6 doi: 10.1016/S2468-1253(24)00080-3. PMID: 38723644
Amirneni S, Haep N, Gad MA, Soto-Gutierrez A, Squires JE, Florentino RM
World J Gastroenterol 2020 Dec 21;26(47):7470-7484. doi: 10.3748/wjg.v26.i47.7470. PMID: 33384548Free PMC Article
Feldman AG, Sokol RJ
Semin Pediatr Surg 2020 Aug;29(4):150945. Epub 2020 Jul 23 doi: 10.1016/j.sempedsurg.2020.150945. PMID: 32861449Free PMC Article
Baker A, Kerkar N, Todorova L, Kamath BM, Houwen RHJ
Clin Res Hepatol Gastroenterol 2019 Feb;43(1):20-36. Epub 2018 Sep 17 doi: 10.1016/j.clinre.2018.07.010. PMID: 30236549
Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E
Orphanet J Rare Dis 2009 Jan 8;4:1. doi: 10.1186/1750-1172-4-1. PMID: 19133130Free PMC Article

Diagnosis

Feldman AG, Sokol RJ
Semin Pediatr Surg 2020 Aug;29(4):150945. Epub 2020 Jul 23 doi: 10.1016/j.sempedsurg.2020.150945. PMID: 32861449Free PMC Article
Baker A, Kerkar N, Todorova L, Kamath BM, Houwen RHJ
Clin Res Hepatol Gastroenterol 2019 Feb;43(1):20-36. Epub 2018 Sep 17 doi: 10.1016/j.clinre.2018.07.010. PMID: 30236549
Bull LN, Thompson RJ
Clin Liver Dis 2018 Nov;22(4):657-669. Epub 2018 Aug 3 doi: 10.1016/j.cld.2018.06.003. PMID: 30266155
Gonzales E, Spraul A, Jacquemin E
Eur J Hum Genet 2014 Apr;22(4) Epub 2013 Sep 4 doi: 10.1038/ejhg.2013.188. PMID: 24002166Free PMC Article
Gonzales E, Spraul A, Jacquemin E
Eur J Hum Genet 2014 Apr;22(4) Epub 2013 Aug 28 doi: 10.1038/ejhg.2013.186. PMID: 23982690Free PMC Article

Therapy

Miethke AG, Moukarzel A, Porta G, Covarrubias Esquer J, Czubkowski P, Ordonez F, Mosca A, Aqul AA, Squires RH, Sokal E, D'Agostino D, Baumann U, D'Antiga L, Kasi N, Laborde N, Arikan C, Lin CH, Gilmour S, Mittal N, Chiou FK, Horslen SP, Huber WD, Jaecklin T, Nunes T, Lascau A, Longpre L, Mogul DB, Garner W, Vig P, Hupertz VF, Gonzalez-Peralta RP, Ekong U, Hartley J, Laverdure N, Ovchinsky N, Thompson RJ
Lancet Gastroenterol Hepatol 2024 Jul;9(7):620-631. Epub 2024 May 6 doi: 10.1016/S2468-1253(24)00080-3. PMID: 38723644
Kavallar AM, Mayerhofer C, Aldrian D, Okamoto T, Müller T, Vogel GF
Hepatol Commun 2023 Oct 1;7(10) Epub 2023 Sep 27 doi: 10.1097/HC9.0000000000000286. PMID: 37756114Free PMC Article
Haney S, Harper J, Truemper E
WMJ 2019 Apr;118(1):47-48. PMID: 31083836
Baker A, Kerkar N, Todorova L, Kamath BM, Houwen RHJ
Clin Res Hepatol Gastroenterol 2019 Feb;43(1):20-36. Epub 2018 Sep 17 doi: 10.1016/j.clinre.2018.07.010. PMID: 30236549
Jacquemin E
Clin Liver Dis 2000 Nov;4(4):753-63. doi: 10.1016/s1089-3261(05)70139-2. PMID: 11232355

Prognosis

Miethke AG, Moukarzel A, Porta G, Covarrubias Esquer J, Czubkowski P, Ordonez F, Mosca A, Aqul AA, Squires RH, Sokal E, D'Agostino D, Baumann U, D'Antiga L, Kasi N, Laborde N, Arikan C, Lin CH, Gilmour S, Mittal N, Chiou FK, Horslen SP, Huber WD, Jaecklin T, Nunes T, Lascau A, Longpre L, Mogul DB, Garner W, Vig P, Hupertz VF, Gonzalez-Peralta RP, Ekong U, Hartley J, Laverdure N, Ovchinsky N, Thompson RJ
Lancet Gastroenterol Hepatol 2024 Jul;9(7):620-631. Epub 2024 May 6 doi: 10.1016/S2468-1253(24)00080-3. PMID: 38723644
Guerrero L, Carmona-Rodríguez L, Santos FM, Ciordia S, Stark L, Hierro L, Pérez-Montero P, Vicent D, Corrales FJ
Biofactors 2024 Jul-Aug;50(4):794-809. Epub 2024 Jan 29 doi: 10.1002/biof.2041. PMID: 38284625
Baker A, Kerkar N, Todorova L, Kamath BM, Houwen RHJ
Clin Res Hepatol Gastroenterol 2019 Feb;43(1):20-36. Epub 2018 Sep 17 doi: 10.1016/j.clinre.2018.07.010. PMID: 30236549
Khan Z, Orr A, Michalopoulos GK, Ranganathan S
Pediatr Dev Pathol 2017 Jan-Feb;20(1):16-27. doi: 10.1177/1093526616686244. PMID: 28276299Free PMC Article
Linton KJ
Biochem Soc Trans 2015 Oct;43(5):1003-10. doi: 10.1042/BST20150132. PMID: 26517915

Clinical prediction guides

Miethke AG, Moukarzel A, Porta G, Covarrubias Esquer J, Czubkowski P, Ordonez F, Mosca A, Aqul AA, Squires RH, Sokal E, D'Agostino D, Baumann U, D'Antiga L, Kasi N, Laborde N, Arikan C, Lin CH, Gilmour S, Mittal N, Chiou FK, Horslen SP, Huber WD, Jaecklin T, Nunes T, Lascau A, Longpre L, Mogul DB, Garner W, Vig P, Hupertz VF, Gonzalez-Peralta RP, Ekong U, Hartley J, Laverdure N, Ovchinsky N, Thompson RJ
Lancet Gastroenterol Hepatol 2024 Jul;9(7):620-631. Epub 2024 May 6 doi: 10.1016/S2468-1253(24)00080-3. PMID: 38723644
Vasudevan AK, Shanmugam N, Rammohan A, Valamparampil JJ, Rinaldhy K, Menon J, Thambithurai R, Namasivayam S, Kaliamoorthy I, Rela M
Pediatr Transplant 2023 Dec;27(8):e14600. Epub 2023 Sep 7 doi: 10.1111/petr.14600. PMID: 37675889
Mighiu C, O'Hara S, Ferri Grazzi E, Murray KF, Schattenberg JM, Ventura E, Karakaidos M, Taylor A, Brrang H, Dhawan A, Willemse J, Finnegan A
Orphanet J Rare Dis 2022 Feb 2;17(1):32. doi: 10.1186/s13023-022-02177-0. PMID: 35109890Free PMC Article
Varol Fİ, Selimoğlu MA, Güngör Ş, Yılmaz S, Tekedereli İ
Arab J Gastroenterol 2021 Dec;22(4):310-315. Epub 2021 Nov 25 doi: 10.1016/j.ajg.2021.05.021. PMID: 34840097
Khan Z, Orr A, Michalopoulos GK, Ranganathan S
Pediatr Dev Pathol 2017 Jan-Feb;20(1):16-27. doi: 10.1177/1093526616686244. PMID: 28276299Free PMC Article

Recent systematic reviews

Kavallar AM, Mayerhofer C, Aldrian D, Okamoto T, Müller T, Vogel GF
Hepatol Commun 2023 Oct 1;7(10) Epub 2023 Sep 27 doi: 10.1097/HC9.0000000000000286. PMID: 37756114Free PMC Article
Baker A, Kerkar N, Todorova L, Kamath BM, Houwen RHJ
Clin Res Hepatol Gastroenterol 2019 Feb;43(1):20-36. Epub 2018 Sep 17 doi: 10.1016/j.clinre.2018.07.010. PMID: 30236549

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