Search for a rare disease
Other search option(s)
Congenital bile acid synthesis defect type 4
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.
ORPHA:79095Classification level: Disorder
- 2-methylacyl-CoA racemase deficiency
- AMACR deficiency
- Alpha-methyl-acyl-CoA racemase deficiency
- Liver disease-retinitis pigmentosa-polyneuropathy-epilepsy syndrome
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal recessive
- Age of onset: All ages
- ICD-10: K76.8
- OMIM: 214950 614307
- UMLS: C1858328 C3280428
- MeSH: C535444
- GARD: 10046
- MedDRA: -
Five cases have been reported to date: two siblings presenting with neonatal cholestasis and three adults with neurological disease.
The clinical presentation of this defect varies. Infants present with severe fat and fat-soluble vitamin deficiencies, hematochezia and mild cholestasis, whereas adults present with various neurological disorders. It is possible that the adults had undocumented mild liver disease and fat-soluble vitamin deficiency in earlier life that led to neurological disease.
BAS defect type 4 is caused by a mutation in the AMACR gene (5p13.2-q11.1).
Diagnosis is based on liquid secondary ionization mass spectrometry (LSIMS), gas chromatography-mass spectrometry (GC-MS) and electrospray ionization-tandem mass spectrometry analysis of urine, serum and bile.
Transmission is autosomal recessive.
Management and treatment
Treatment is based on primary bile acid therapy with cholic acid. Dietary restriction of phytanic and pristanic acids is likely to be necessary in the long term to prevent neurotoxicity.
- Clinical practice guidelines
- Français (2019, pdf)