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Congenital bile acid synthesis defect 1(CBAS1)

MedGen UID:
335883
Concept ID:
C1843116
Disease or Syndrome
Synonyms: 3-alpha beta-hydroxy-delta-5-c27-steroid oxidoreductase, deficiency of; 3-BETA-HYDROXY-DELTA-5-C27-STEROID OXIDOREDUCTASE DEFICIENCY; CBAS1
SNOMED CT: 3-Beta-hydroxy-delta-5-C27-steroid dehydrogenase deficiency (238033007); Congenital bile acid synthesis defect type 1 (238033007)
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): HSD3B7 (16p11.2)
 
Monarch Initiative: MONDO:0011906
OMIM®: 607765
Orphanet: ORPHA79301

Definition

Congenital defects of bile acid synthesis are autosomal recessive disorders characterized by neonatal onset of progressive liver disease with cholestatic jaundice and malabsorption of lipids and lipid-soluble vitamins from the gastrointestinal tract resulting from a primary failure to synthesize bile acids. Affected infants show failure to thrive and secondary coagulopathy. In most forms of the disorder, there is a favorable response to oral bile acid therapy (summary by Cheng et al., 2003). Genetic Heterogeneity of Congenital Defects in Bile Acid Synthesis There are several disorders that result from defects in bile acid synthesis. See CBAS2 (235555), caused by mutation in the delta(4)-3-oxosteroid 5-beta-reductase gene (AKR1D1; 604741) on chromosome 7q33; CBAS3 (613812), caused by mutation in the 7-alpha hydroxylase gene (CYP7B1; 603711) on chromosome 8q12; CBAS4 (214950), caused by mutation in the AMACR gene (604489) on chromosome 5p13; CBAS5 (616278), caused by mutation in the ABCD3 gene (170995) on chromosome 1p21; and CBAS6 (617308), caused by mutation in the ACOX2 gene (601641) on chromosome 3p14. See also progressive familial intrahepatic cholestasis (PFIC1; 211600), which has a similar phenotype. [from OMIM]

Additional description

From MedlinePlus Genetics
Congenital bile acid synthesis defect type 1 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 1 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 1 often develop during the first weeks of life, but they can begin anytime from infancy into adulthood. Affected infants often 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 an additional feature of congenital bile acid synthesis defect type 1. As the condition progresses, affected individuals can develop liver abnormalities including an enlarged liver (hepatomegaly), inflammation, or chronic liver disease (cirrhosis). The spleen may also become enlarged (splenomegaly). The inability to absorb certain fat-soluble vitamins (vitamin D in particular) can result in softening and weakening of the bones (rickets) in some individuals.

If left untreated, congenital bile acid synthesis defect type 1 often leads to cirrhosis and death in childhood.  https://medlineplus.gov/genetics/condition/congenital-bile-acid-synthesis-defect-type-1

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.
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.
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.
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.
Fat malabsorption
MedGen UID:
108215
Concept ID:
C0554103
Pathologic Function
Abnormality of the absorption of fat from the gastrointestinal tract.
Acholic stools
MedGen UID:
436478
Concept ID:
C2675627
Finding
Clay colored stools lacking bile pigment.
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.
Rickets
MedGen UID:
48470
Concept ID:
C0035579
Disease or Syndrome
Rickets is divided into two major categories including calcipenic and phosphopenic. Hypophosphatemia is described as a common manifestation of both categories. Hypophosphatemic rickets is the most common type of rickets that is characterized by low levels of serum phosphate, resistance to ultraviolet radiation or vitamin D intake. There are several issues involved in hypophosphatemic rickets such as calcium, vitamin D, phosphorus deficiencies. Moreover, other disorder can be associated with its occurrence such as absorption defects due to pancreatic, intestinal, gastric, and renal disorders and hepatobiliary disease. Symptoms are usually seen in childhood and can be varied in severity. Severe forms may be linked to bowing of the legs, poor bone growth, and short stature as well as joint and bone pain. Hypophosphatemic rickets are associated with renal excretion of phosphate, hypophosphatemia, and mineral defects in bones. The familial type of the disease is the most common type of rickets.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Hypocholesterolemia
MedGen UID:
57479
Concept ID:
C0151718
Disease or Syndrome
An decreased concentration of cholesterol in the blood.
Conjugated hyperbilirubinemia
MedGen UID:
82787
Concept ID:
C0268307
Disease or Syndrome
Abnormally high level of conjugated bilirubin in the blood.
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.
Reduced C27 3beta-HSD activity in cultured fibroblasts
MedGen UID:
1054256
Concept ID:
CN377973
Finding
Concentration or activity of 3beta-hydroxy-delta5-C27-steroid oxidoreductase (C27 3beta-HSD) as measured in cultured fibroblasts is below the limits of normal.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCongenital bile acid synthesis defect 1
Follow this link to review classifications for Congenital bile acid synthesis defect 1 in Orphanet.

Professional guidelines

PubMed

Fang Y, Zhang Z, Zhao Y, Sun G, Peng M, Liu C, Yi G, Zhao K, Yang H
Clin Chim Acta 2023 Apr 1;544:117330. Epub 2023 Apr 8 doi: 10.1016/j.cca.2023.117330. PMID: 37037297
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
Sherlock S
Br Med J 1968 Aug 31;3(5617):515-21. doi: 10.1136/bmj.3.5617.515. PMID: 4971054Free PMC Article

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
Ballout RA, Livinski A, Fu YP, Steiner RD, Remaley AT
Cochrane Database Syst Rev 2022 Nov 14;11(11):CD013521. doi: 10.1002/14651858.CD013521.pub2. PMID: 36373961Free PMC Article
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

Ballout RA, Livinski A, Fu YP, Steiner RD, Remaley AT
Cochrane Database Syst Rev 2022 Nov 14;11(11):CD013521. doi: 10.1002/14651858.CD013521.pub2. PMID: 36373961Free PMC Article
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
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
Ballout RA, Livinski A, Fu YP, Steiner RD, Remaley AT
Cochrane Database Syst Rev 2022 Nov 14;11(11):CD013521. doi: 10.1002/14651858.CD013521.pub2. PMID: 36373961Free 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
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
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
Fang Y, Zhang Z, Zhao Y, Sun G, Peng M, Liu C, Yi G, Zhao K, Yang H
Clin Chim Acta 2023 Apr 1;544:117330. Epub 2023 Apr 8 doi: 10.1016/j.cca.2023.117330. PMID: 37037297
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
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
Ballout RA, Livinski A, Fu YP, Steiner RD, Remaley AT
Cochrane Database Syst Rev 2022 Nov 14;11(11):CD013521. doi: 10.1002/14651858.CD013521.pub2. PMID: 36373961Free PMC Article

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