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Cholestasis, progressive familial intrahepatic, 12(PFIC12)

MedGen UID:
1824084
Concept ID:
C5774311
Disease or Syndrome
Synonyms: CHOLESTASIS, ISOLATED LOW-GGT; PFIC12
 
Gene (location): VPS33B (15q26.1)
 
Monarch Initiative: MONDO:0031040
OMIM®: 620010

Definition

Progressive familial intrahepatic cholestasis-12 (PFIC12) is characterized by neonatal-onset jaundice and conjugated hyperbilirubinemia, associated with intense pruritus. Transaminases are mildly elevated but GGT (see 612346) is normal. Hepatosplenomegaly and mildly prolonged activated partial thromboplastin time (APTT) have been observed in some patients (Qiu et al., 2019). [from OMIM]

Clinical features

From HPO
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Cholestasis
MedGen UID:
925
Concept ID:
C0008370
Disease or Syndrome
Impairment of bile flow due to obstruction in bile ducts.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Prolonged partial thromboplastin time
MedGen UID:
66815
Concept ID:
C0240671
Finding
Increased time to coagulation in the partial thromboplastin time (PTT) test, a measure of the intrinsic and common coagulation pathways. Phospholipid, and activator, and calcium are mixed into an anticoagulated plasma sample, and the time is measured until a thrombus forms.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Elevated circulating aspartate aminotransferase concentration
MedGen UID:
57497
Concept ID:
C0151904
Finding
The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal.
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
Concept ID:
C0151905
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
Conjugated hyperbilirubinemia
MedGen UID:
82787
Concept ID:
C0268307
Disease or Syndrome
Abnormally high level of conjugated bilirubin in the blood.
Hyperbilirubinemia
MedGen UID:
86321
Concept ID:
C0311468
Finding
An increased amount of bilirubin in the blood.
Increased serum bile acid concentration
MedGen UID:
868605
Concept ID:
C4023004
Finding
An increase in the concentration of bile acid in the blood.
Pruritus
MedGen UID:
19534
Concept ID:
C0033774
Sign or Symptom
Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased disposition to experience pruritus.

Professional guidelines

PubMed

Cheng K, Rosenthal P
Hepatol Commun 2023 Dec 1;7(12) Epub 2023 Dec 7 doi: 10.1097/HC9.0000000000000314. PMID: 38055640Free 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
van Wessel DBE, Thompson RJ, Gonzales E, Jankowska I, Shneider BL, Sokal E, Grammatikopoulos T, Kadaristiana A, Jacquemin E, Spraul A, Lipiński P, Czubkowski P, Rock N, Shagrani M, Broering D, Algoufi T, Mazhar N, Nicastro E, Kelly D, Nebbia G, Arnell H, Fischler B, Hulscher JBF, Serranti D, Arikan C, Debray D, Lacaille F, Goncalves C, Hierro L, Muñoz Bartolo G, Mozer-Glassberg Y, Azaz A, Brecelj J, Dezsőfi A, Luigi Calvo P, Krebs-Schmitt D, Hartleif S, van der Woerd WL, Wang JS, Li LT, Durmaz Ö, Kerkar N, Hørby Jørgensen M, Fischer R, Jimenez-Rivera C, Alam S, Cananzi M, Laverdure N, Targa Ferreira C, Ordonez F, Wang H, Sency V, Mo Kim K, Chen HL, Carvalho E, Fabre A, Quintero Bernabeu J, Alonso EM, Sokol RJ, Suchy FJ, Loomes KM, McKiernan PJ, Rosenthal P, Turmelle Y, Rao GS, Horslen S, Kamath BM, Rogalidou M, Karnsakul WW, Hansen B, Verkade HJ; Natural Course and Prognosis of PFIC and Effect of Biliary Diversion Consortium
Hepatology 2021 Aug;74(2):892-906. Epub 2021 Jul 13 doi: 10.1002/hep.31787. PMID: 33666275Free PMC Article

Recent clinical studies

Etiology

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
Thompson RJ, Arnell H, Artan R, Baumann U, Calvo PL, Czubkowski P, Dalgic B, D'Antiga L, Durmaz Ö, Fischler B, Gonzalès E, Grammatikopoulos T, Gupte G, Hardikar W, Houwen RHJ, Kamath BM, Karpen SJ, Kjems L, Lacaille F, Lachaux A, Lainka E, Mack CL, Mattsson JP, McKiernan P, Özen H, Rajwal SR, Roquelaure B, Shagrani M, Shteyer E, Soufi N, Sturm E, Tessier ME, Verkade HJ, Horn P
Lancet Gastroenterol Hepatol 2022 Sep;7(9):830-842. Epub 2022 Jul 1 doi: 10.1016/S2468-1253(22)00093-0. PMID: 35780807
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
Jones-Hughes T, Campbell J, Crathorne L
Orphanet J Rare Dis 2021 Jun 3;16(1):255. doi: 10.1186/s13023-021-01884-4. PMID: 34082807Free 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

Diagnosis

Cheng K, Rosenthal P
Hepatol Commun 2023 Dec 1;7(12) Epub 2023 Dec 7 doi: 10.1097/HC9.0000000000000314. PMID: 38055640Free PMC Article
Thompson RJ, Arnell H, Artan R, Baumann U, Calvo PL, Czubkowski P, Dalgic B, D'Antiga L, Durmaz Ö, Fischler B, Gonzalès E, Grammatikopoulos T, Gupte G, Hardikar W, Houwen RHJ, Kamath BM, Karpen SJ, Kjems L, Lacaille F, Lachaux A, Lainka E, Mack CL, Mattsson JP, McKiernan P, Özen H, Rajwal SR, Roquelaure B, Shagrani M, Shteyer E, Soufi N, Sturm E, Tessier ME, Verkade HJ, Horn P
Lancet Gastroenterol Hepatol 2022 Sep;7(9):830-842. Epub 2022 Jul 1 doi: 10.1016/S2468-1253(22)00093-0. PMID: 35780807
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
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
van der Woerd WL, van Mil SW, Stapelbroek JM, Klomp LW, van de Graaf SF, Houwen RH
Best Pract Res Clin Gastroenterol 2010 Oct;24(5):541-53. doi: 10.1016/j.bpg.2010.07.010. PMID: 20955958

Therapy

Chen R, Yang FX, Tan YF, Deng M, Li H, Xu Y, Ouyang WX, Song YZ
Orphanet J Rare Dis 2022 Dec 22;17(1):445. doi: 10.1186/s13023-022-02597-y. PMID: 36550572Free PMC Article
Thompson RJ, Arnell H, Artan R, Baumann U, Calvo PL, Czubkowski P, Dalgic B, D'Antiga L, Durmaz Ö, Fischler B, Gonzalès E, Grammatikopoulos T, Gupte G, Hardikar W, Houwen RHJ, Kamath BM, Karpen SJ, Kjems L, Lacaille F, Lachaux A, Lainka E, Mack CL, Mattsson JP, McKiernan P, Özen H, Rajwal SR, Roquelaure B, Shagrani M, Shteyer E, Soufi N, Sturm E, Tessier ME, Verkade HJ, Horn P
Lancet Gastroenterol Hepatol 2022 Sep;7(9):830-842. Epub 2022 Jul 1 doi: 10.1016/S2468-1253(22)00093-0. PMID: 35780807
Loomes KM, Squires RH, Kelly D, Rajwal S, Soufi N, Lachaux A, Jankowska I, Mack C, Setchell KDR, Karthikeyan P, Kennedy C, Dorenbaum A, Desai NK, Garner W, Jaecklin T, Vig P, Miethke A, Thompson RJ
Hepatol Commun 2022 Sep;6(9):2379-2390. Epub 2022 May 4 doi: 10.1002/hep4.1980. PMID: 35507739Free 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
van der Woerd WL, van Mil SW, Stapelbroek JM, Klomp LW, van de Graaf SF, Houwen RH
Best Pract Res Clin Gastroenterol 2010 Oct;24(5):541-53. doi: 10.1016/j.bpg.2010.07.010. PMID: 20955958

Prognosis

Jones-Hughes T, Campbell J, Crathorne L
Orphanet J Rare Dis 2021 Jun 3;16(1):255. doi: 10.1186/s13023-021-01884-4. PMID: 34082807Free PMC Article
van Wessel DBE, Thompson RJ, Gonzales E, Jankowska I, Shneider BL, Sokal E, Grammatikopoulos T, Kadaristiana A, Jacquemin E, Spraul A, Lipiński P, Czubkowski P, Rock N, Shagrani M, Broering D, Algoufi T, Mazhar N, Nicastro E, Kelly D, Nebbia G, Arnell H, Fischler B, Hulscher JBF, Serranti D, Arikan C, Debray D, Lacaille F, Goncalves C, Hierro L, Muñoz Bartolo G, Mozer-Glassberg Y, Azaz A, Brecelj J, Dezsőfi A, Luigi Calvo P, Krebs-Schmitt D, Hartleif S, van der Woerd WL, Wang JS, Li LT, Durmaz Ö, Kerkar N, Hørby Jørgensen M, Fischer R, Jimenez-Rivera C, Alam S, Cananzi M, Laverdure N, Targa Ferreira C, Ordonez F, Wang H, Sency V, Mo Kim K, Chen HL, Carvalho E, Fabre A, Quintero Bernabeu J, Alonso EM, Sokol RJ, Suchy FJ, Loomes KM, McKiernan PJ, Rosenthal P, Turmelle Y, Rao GS, Horslen S, Kamath BM, Rogalidou M, Karnsakul WW, Hansen B, Verkade HJ; Natural Course and Prognosis of PFIC and Effect of Biliary Diversion Consortium
Hepatology 2021 Aug;74(2):892-906. Epub 2021 Jul 13 doi: 10.1002/hep.31787. PMID: 33666275Free PMC Article
Okamoto T, Sonoda M, Ogawa E, Ito S, Togawa T, Hayashi H, Okajima H, Uemoto S
J Pediatr Gastroenterol Nutr 2021 Mar 1;72(3):425-429. doi: 10.1097/MPG.0000000000002983. PMID: 33264179
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
Morotti RA, Suchy FJ, Magid MS
Semin Liver Dis 2011 Feb;31(1):3-10. Epub 2011 Feb 22 doi: 10.1055/s-0031-1272831. PMID: 21344347

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
Thompson RJ, Arnell H, Artan R, Baumann U, Calvo PL, Czubkowski P, Dalgic B, D'Antiga L, Durmaz Ö, Fischler B, Gonzalès E, Grammatikopoulos T, Gupte G, Hardikar W, Houwen RHJ, Kamath BM, Karpen SJ, Kjems L, Lacaille F, Lachaux A, Lainka E, Mack CL, Mattsson JP, McKiernan P, Özen H, Rajwal SR, Roquelaure B, Shagrani M, Shteyer E, Soufi N, Sturm E, Tessier ME, Verkade HJ, Horn P
Lancet Gastroenterol Hepatol 2022 Sep;7(9):830-842. Epub 2022 Jul 1 doi: 10.1016/S2468-1253(22)00093-0. PMID: 35780807
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
Jones-Hughes T, Campbell J, Crathorne L
Orphanet J Rare Dis 2021 Jun 3;16(1):255. doi: 10.1186/s13023-021-01884-4. PMID: 34082807Free PMC Article

Recent systematic reviews

Jones-Hughes T, Campbell J, Crathorne L
Orphanet J Rare Dis 2021 Jun 3;16(1):255. doi: 10.1186/s13023-021-01884-4. PMID: 34082807Free 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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