Inborn defects in BA synthesis: side chain shortening and conjugation
| Gene | Protein | Clinical features | Treatment | Ref. | Animal models |
|---|---|---|---|---|---|
| CYP27A1 | CYP27A1 | Children: neonatal cholestasis, diarrhea, cataracts, growth retardationAdults: xanthomas, neuropsychiatric symptoms (ataxia, dementia) | CDCA | [48, 54] | [50–53] |
| PEX | Several peroxisomal proteins | Liver dysfunction, neurological abnormalities, hearing and vision impairment, adrenocortical dysfunction | Symptomatic or supportive therapies | [56, 57] | [58–60] |
| ABCD3 | PMP70 | Hepatic dysfunction, hepatosplenomegaly | N.D. | [61] | [61, 87] |
| AMACR | AMACR | Children: malabsorption of fat-soluble vitamins, coagulation disorders, cholestasis, hepatitisAdults: sensory and motor degenerative neuropathy | CA | [63–66] | [67] |
| ACOX2 | ACOX2 | Hypertransaminasemia and severe hepatic and neurological alterations | CholestyramineUDCA | [69–72] | [73, 74] |
| HSD17B4 | DBP | Hypotonia, delayed growth and psychomotor development, visual and auditory defects. Hepatomegaly, fibrosis | N.D. | [75] | [76, 77] |
| SCP2 | SCPx | Fertility abnormalities. Brain lesions with motor disorders | Phytanic acid-restricted diet | [78, 79] | [80] |
| SLC27A5 | BACS | No signs of liver disease | N.D. | [81] | [82, 83] |
| BAAT | BAAT | Neonatal cholestasis. Malabsorption of fat-soluble vitamins. Rickets | GCA | [84, 86] | [85] |
ABCD3: ATP-binding cassette subfamily D member 3; ACOX2: acyl-coenzyme A (CoA) oxidase 2; AMACR: α-methyl acyl-CoA racemase; BA: bile acid; BAAT: BA CoA: amino acid N-acyl transferase; BACS: BA-CoA synthetase; CYP27A1: sterol 27-hydroxylase; DBP: D-bifunctional protein; PEX: peroxisomal biogenesis factor or peroxin; PMP70: peroxisomal membrane protein 70; SCP2: sterol carrier protein 2