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Congenital bile acid synthesis defect 4(CBAS4)

MedGen UID:
388039
Concept ID:
C1858328
Disease or Syndrome
Synonyms: CBAS4; Cholestasis, intrahepatic, with defective conversion of; CHOLESTASIS, INTRAHEPATIC, WITH DEFECTIVE CONVERSION OF TRIHYDROXYCOPROSTANIC ACID TO CHOLIC ACID; Trihydroxycoprostanic acid in bile; Trihydroxycoprostanic acid to cholic acid
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): AMACR (5p13.2)
 
Monarch Initiative: MONDO:0008967
OMIM®: 214950
Orphanet: ORPHA79095

Definition

Congenital bile acid synthesis defect type 4 (BAS defect type 4) is an anomaly of bile acid synthesis (see this term) characterized by mild cholestatic liver disease, fat malabsorption and/or neurological disease. [from ORDO]

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
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.
Hematochezia
MedGen UID:
5481
Concept ID:
C0018932
Disease or Syndrome
The passage of fresh (red) blood per anus, usually in or with stools. Most rectal bleeding comes from the colon, rectum, or anus.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Giant cell hepatitis
MedGen UID:
45030
Concept ID:
C0027613
Disease or Syndrome
Chronic hepatitis characterized by parenchymal inflammation with formation of large multinucleated hepatocytes in response to a variety of insults to the liver.
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.
Fat malabsorption
MedGen UID:
108215
Concept ID:
C0554103
Pathologic Function
Abnormality of the absorption of fat from the gastrointestinal tract.
Prolonged neonatal jaundice
MedGen UID:
347108
Concept ID:
C1859236
Finding
Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants.
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.
Prolonged prothrombin time
MedGen UID:
208879
Concept ID:
C0853225
Finding
Increased time to coagulation in the prothrombin time test, which is a measure of the extrinsic pathway of coagulation. The results of the prothrombin time test are often expressed in terms of the International normalized ratio (INR), which is calculated as a ratio of the patient's prothrombin time (PT) to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the formula
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 hepatic transaminase concentration
MedGen UID:
116013
Concept ID:
C0235996
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Hyperbilirubinemia
MedGen UID:
86321
Concept ID:
C0311468
Finding
An increased amount of bilirubin in the blood.
Decreased circulating calcifediol concentration
MedGen UID:
868662
Concept ID:
C4023064
Finding
A reduced concentration of calcifediol in the blood. Calcifediol is also known as calcidiol, 25-hydroxycholecalciferol and 25-Hydroxyvitamin D3.
Decreased serum bile acid concentration
MedGen UID:
1813049
Concept ID:
C5676648
Finding
A reduction in the concentration of bile acid in the blood.
Decreased circulating vitamin E concentration
MedGen UID:
1853278
Concept ID:
C5779643
Finding
A reduced concentration of vitamin E in the blood circulation. Vitamin E is a lipophilic vitamin that is also known as alpha-tocopherol.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCongenital bile acid synthesis defect 4
Follow this link to review classifications for Congenital bile acid synthesis defect 4 in Orphanet.

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
Lin Y, Zhang F, Zhang L, Chen L, Zheng S
Stem Cell Res Ther 2022 Mar 21;13(1):114. doi: 10.1186/s13287-022-02795-2. PMID: 35313986Free 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
Subramaniam P, Knisely A, Portmann B, Qureshi SA, Aclimandos WA, Karani JB, Baker AJ
J Pediatr Gastroenterol Nutr 2011 Jan;52(1):84-9. doi: 10.1097/MPG.0b013e3181f1572d. PMID: 21119543

Diagnosis

Zhao J, Qiu YL, Wang L, Li ZD, Xie XB, Lu Y, Setchell KDR, Cheng Y, Xing QH, Wang JS
J Mol Diagn 2023 Apr;25(4):227-233. Epub 2023 Feb 4 doi: 10.1016/j.jmoldx.2023.01.004. PMID: 36739965
Heubi JE, Setchell KDR, Bove KE
Clin Liver Dis 2018 Nov;22(4):671-687. Epub 2018 Aug 22 doi: 10.1016/j.cld.2018.06.006. PMID: 30266156
Subramaniam P, Knisely A, Portmann B, Qureshi SA, Aclimandos WA, Karani JB, Baker AJ
J Pediatr Gastroenterol Nutr 2011 Jan;52(1):84-9. doi: 10.1097/MPG.0b013e3181f1572d. PMID: 21119543
Bove KE, Heubi JE, Balistreri WF, Setchell KD
Pediatr Dev Pathol 2004 Jul-Aug;7(4):315-34. Epub 2004 Jul 15 doi: 10.1007/s10024-002-1201-8. PMID: 15383928
Eyssen H, Eggermont E, van Eldere J, Jaeken J, Parmentier G, Janssen G
Acta Paediatr Scand 1985 Jul;74(4):539-44. doi: 10.1111/j.1651-2227.1985.tb11025.x. PMID: 4024924

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
Gonzales E, Matarazzo L, Franchi-Abella S, Dabadie A, Cohen J, Habes D, Hillaire S, Guettier C, Taburet AM, Myara A, Jacquemin E
Orphanet J Rare Dis 2018 Oct 29;13(1):190. doi: 10.1186/s13023-018-0920-5. PMID: 30373615Free PMC Article
Heubi JE, Setchell KDR, Bove KE
Clin Liver Dis 2018 Nov;22(4):671-687. Epub 2018 Aug 22 doi: 10.1016/j.cld.2018.06.006. PMID: 30266156
Wang HH, Wen FQ, Dai DL, Wang JS, Zhao J, Setchell KD, Shi LN, Zhou SM, Liu SX, Yang QH
World J Gastroenterol 2018 Sep 21;24(35):4086-4092. doi: 10.3748/wjg.v24.i35.4086. PMID: 30254413Free PMC Article
Nagasaka H, Miida T, Yorifuji T, Hirano K, Inui A, Fujisawa T, Tsukahara H, Hayashi H, Inomata Y
Clin Chim Acta 2013 Apr 18;419:52-6. Epub 2013 Feb 8 doi: 10.1016/j.cca.2013.01.016. PMID: 23399721

Prognosis

Lin Y, Zhang F, Zhang L, Chen L, Zheng S
Stem Cell Res Ther 2022 Mar 21;13(1):114. doi: 10.1186/s13287-022-02795-2. PMID: 35313986Free PMC Article
Lemmer A, VanWagner L, Gasanova Z, Helmke S, Everson GT, Ganger D
Congenit Heart Dis 2019 Nov;14(6):978-986. Epub 2019 Aug 1 doi: 10.1111/chd.12831. PMID: 31369200Free PMC Article
Subramaniam P, Knisely A, Portmann B, Qureshi SA, Aclimandos WA, Karani JB, Baker AJ
J Pediatr Gastroenterol Nutr 2011 Jan;52(1):84-9. doi: 10.1097/MPG.0b013e3181f1572d. PMID: 21119543
Bove KE, Heubi JE, Balistreri WF, Setchell KD
Pediatr Dev Pathol 2004 Jul-Aug;7(4):315-34. Epub 2004 Jul 15 doi: 10.1007/s10024-002-1201-8. PMID: 15383928

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
Lin Y, Zhang F, Zhang L, Chen L, Zheng S
Stem Cell Res Ther 2022 Mar 21;13(1):114. doi: 10.1186/s13287-022-02795-2. PMID: 35313986Free PMC Article
Lemmer A, VanWagner L, Gasanova Z, Helmke S, Everson GT, Ganger D
Congenit Heart Dis 2019 Nov;14(6):978-986. Epub 2019 Aug 1 doi: 10.1111/chd.12831. PMID: 31369200Free PMC Article
Gonzales E, Matarazzo L, Franchi-Abella S, Dabadie A, Cohen J, Habes D, Hillaire S, Guettier C, Taburet AM, Myara A, Jacquemin E
Orphanet J Rare Dis 2018 Oct 29;13(1):190. doi: 10.1186/s13023-018-0920-5. PMID: 30373615Free 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

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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