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Congenital bile acid synthesis defect 2(CBAS2)

MedGen UID:
383840
Concept ID:
C1856127
Disease or Syndrome
Synonyms: CBAS2; Cholestasis with delta(4)-3-oxosteroid 5-beta-reductase deficiency
SNOMED CT: Delta-4-3-oxosteroid-5-beta-reductase deficiency (238035000); Congenital bile acid synthesis defect type 2 (238035000)
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): AKR1D1 (7q33)
 
Monarch Initiative: MONDO:0009339
OMIM®: 235555
Orphanet: ORPHA79303

Definition

Congenital bile acid synthesis defect type 2 is a disorder characterized by cholestasis, a condition that impairs the production and release of a digestive fluid called bile from liver cells. Bile is used during digestion to absorb fats and fat-soluble vitamins, such as vitamins A, D, E, and K. People with congenital bile acid synthesis defect type 2 cannot produce (synthesize) bile acids, which are a component of bile that stimulate bile flow and help it absorb fats and fat-soluble vitamins. As a result, an abnormal form of bile is produced.

The signs and symptoms of congenital bile acid synthesis defect type 2 often develop in infancy. Affected infants usually have a failure to gain weight and grow at the expected rate (failure to thrive) and yellowing of the skin and eyes (jaundice) due to impaired bile flow and a buildup of partially formed bile. Excess fat in the feces (steatorrhea) is another feature of congenital bile acid synthesis defect type 2. As the condition progresses, affected individuals can develop liver abnormalities including inflammation or chronic liver disease (cirrhosis). Some individuals with congenital bile acid synthesis defect type 2 cannot absorb certain fat-soluble vitamins, which can result in softening and weakening of the bones (rickets) or problems with blood clotting that lead to prolonged bleeding.

If left untreated, congenital bile acid synthesis defect type 2 typically leads to cirrhosis and death in childhood. [from MedlinePlus Genetics]

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.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
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.
Steatorrhea
MedGen UID:
20948
Concept ID:
C0038238
Finding
Greater than normal amounts of fat in the feces. This is a result of malabsorption of lipids in the small intestine and results in frothy foul-smelling fecal matter that floats.
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.
Abnormality of the coagulation cascade
MedGen UID:
604
Concept ID:
C0005779
Disease or Syndrome
An abnormality of the coagulation cascade, which is comprised of the contact activation pathway (also known as the intrinsic pathway) and the tissue factor pathway (also known as the extrinsic pathway) as well as cofactors and regulators.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Hyperbilirubinemia
MedGen UID:
86321
Concept ID:
C0311468
Finding
An increased amount of bilirubin in the blood.
Elevated circulating alkaline phosphatase concentration
MedGen UID:
727252
Concept ID:
C1314665
Finding
Abnormally increased serum levels of alkaline phosphatase activity.
Elevated circulating hepatic transaminase concentration
MedGen UID:
338525
Concept ID:
C1848701
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCongenital bile acid synthesis defect 2
Follow this link to review classifications for Congenital bile acid synthesis defect 2 in Orphanet.

Professional guidelines

PubMed

Miyano T, Yamashiro Y, Shimizu T, Arai T, Suruga T, Hayasawa H
J Pediatr Surg 1986 Mar;21(3):277-81. doi: 10.1016/s0022-3468(86)80854-5. PMID: 3083086

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
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
Kahn E
Pediatr Dev Pathol 2004 Mar-Apr;7(2):109-24. Epub 2004 Mar 4 doi: 10.1007/s10024-003-0307-y. PMID: 14994122
Colombo C, Okolicsanyi L, Strazzabosco M
Dig Liver Dis 2000 Mar;32(2):152-9. doi: 10.1016/s1590-8658(00)80403-x. PMID: 10975791

Diagnosis

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
Gioiello A, Cerra B, Zhang W, Vallerini GP, Costantino G, De Franco F, Passeri D, Pellicciari R, Setchell KD
J Steroid Biochem Mol Biol 2014 Oct;144 Pt B:348-60. Epub 2014 Jun 19 doi: 10.1016/j.jsbmb.2014.06.008. PMID: 24954360
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
Kahn E
Pediatr Dev Pathol 2004 Mar-Apr;7(2):109-24. Epub 2004 Mar 4 doi: 10.1007/s10024-003-0307-y. PMID: 14994122
Colombo C, Okolicsanyi L, Strazzabosco M
Dig Liver Dis 2000 Mar;32(2):152-9. doi: 10.1016/s1590-8658(00)80403-x. PMID: 10975791

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
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
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

Prognosis

Durin Z, Dubail J, Layotte A, Legrand D, Cormier-Daire V, Foulquier F
Hum Genet 2022 Jul;141(7):1287-1298. Epub 2022 Jan 8 doi: 10.1007/s00439-021-02420-x. PMID: 34999954
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
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
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
Durin Z, Dubail J, Layotte A, Legrand D, Cormier-Daire V, Foulquier F
Hum Genet 2022 Jul;141(7):1287-1298. Epub 2022 Jan 8 doi: 10.1007/s00439-021-02420-x. PMID: 34999954
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
Suchy FJ, Bucuvalas JC, Novak DA
Semin Liver Dis 1987 May;7(2):77-84. doi: 10.1055/s-2008-1040567. PMID: 3303347

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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