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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

Recent clinical studies

Etiology

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
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
Wei CS, Becher N, Friis JB, Ott P, Vogel I, Grønbæk H
World J Gastroenterol 2020 Feb 7;26(5):550-561. doi: 10.3748/wjg.v26.i5.550. PMID: 32089630Free PMC Article
Kremer AE, Gonzales E, Schaap FG, Oude Elferink RP, Jacquemin E, Beuers U
J Pediatr Gastroenterol Nutr 2016 Apr;62(4):530-5. doi: 10.1097/MPG.0000000000001044. PMID: 26628447

Diagnosis

Al Housni S, Al-Thihli K, Rahmatalla D, Wali Y, Al Rawahi Y
Sultan Qaboos Univ Med J 2023 Nov;23(4):543-546. Epub 2023 Nov 30 doi: 10.18295/squmj.8.2022.052. PMID: 38090248Free PMC Article
Wei CS, Becher N, Friis JB, Ott P, Vogel I, Grønbæk H
World J Gastroenterol 2020 Feb 7;26(5):550-561. doi: 10.3748/wjg.v26.i5.550. PMID: 32089630Free PMC Article
Vitale G, Gitto S, Raimondi F, Mattiaccio A, Mantovani V, Vukotic R, D'Errico A, Seri M, Russell RB, Andreone P
J Gastroenterol 2018 Aug;53(8):945-958. Epub 2017 Dec 13 doi: 10.1007/s00535-017-1423-1. PMID: 29238877
Devictor D, Tissieres P, Afanetti M, Debray D
Clin Res Hepatol Gastroenterol 2011 Jun;35(6-7):430-7. Epub 2011 Apr 30 doi: 10.1016/j.clinre.2011.03.005. PMID: 21531191

Therapy

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

Prognosis

Vitale G, Gitto S, Raimondi F, Mattiaccio A, Mantovani V, Vukotic R, D'Errico A, Seri M, Russell RB, Andreone P
J Gastroenterol 2018 Aug;53(8):945-958. Epub 2017 Dec 13 doi: 10.1007/s00535-017-1423-1. PMID: 29238877

Clinical prediction guides

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
Vitale G, Gitto S, Raimondi F, Mattiaccio A, Mantovani V, Vukotic R, D'Errico A, Seri M, Russell RB, Andreone P
J Gastroenterol 2018 Aug;53(8):945-958. Epub 2017 Dec 13 doi: 10.1007/s00535-017-1423-1. PMID: 29238877
Kremer AE, Gonzales E, Schaap FG, Oude Elferink RP, Jacquemin E, Beuers U
J Pediatr Gastroenterol Nutr 2016 Apr;62(4):530-5. doi: 10.1097/MPG.0000000000001044. PMID: 26628447

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

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