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Congenital bile acid synthesis defect 6(CBAS6)

MedGen UID:
934591
Concept ID:
C4310624
Disease or Syndrome
Synonyms: BILE ACID SYNTHESIS DEFECT, CONGENITAL, 6; CBAS6
 
Gene (location): ACOX2 (3p14.3)
 
Monarch Initiative: MONDO:0015015
OMIM®: 617308

Definition

Congenital bile acid synthesis defect-6 (CBAS6) is characterized by persistent hypertransaminasemia and accumulation of C27 bile acids (summary by Alonso-Pena et al., 2022). For a general phenotypic description and a discussion of genetic heterogeneity of congenital bile acid synthesis defects, see CBAS1 (607765). [from OMIM]

Clinical features

From HPO
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.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Slurred speech
MedGen UID:
65885
Concept ID:
C0234518
Finding
Abnormal coordination of muscles involved in speech.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Decreased circulating vitamin D concentration
MedGen UID:
12114
Concept ID:
C0042870
Disease or Syndrome
The concentration of vitamin D in the blood circulation is below the lower limit of normal.
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).
Hypolipidemia
MedGen UID:
575275
Concept ID:
C0342892
Pathologic Function
abnormally decreased amount of fat in the blood.
Vertical supranuclear gaze palsy
MedGen UID:
334385
Concept ID:
C1843369
Disease or Syndrome
A supranuclear gaze palsy is an inability to look in a vertical direction as a result of cerebral impairment. There is a loss of the voluntary aspect of eye movements, but, as the brainstem is still intact, all the reflex conjugate eye movements are normal.

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
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
Tiribelli C, Ostrow JD
Hepatology 1996 Nov;24(5):1296-311. doi: 10.1002/hep.510240551. PMID: 8903413

Diagnosis

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

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

Prognosis

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
Mathis RK, Watkins JB, Szczepanik-Van Leeuwen P, Lott IT
Gastroenterology 1980 Dec;79(6):1311-7. PMID: 7439636

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
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
Mathis RK, Watkins JB, Szczepanik-Van Leeuwen P, Lott IT
Gastroenterology 1980 Dec;79(6):1311-7. PMID: 7439636

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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