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, 87]|
|AMACR||AMACR||Children: malabsorption of fat-soluble vitamins, coagulation disorders, cholestasis, hepatitisAdults: sensory and motor degenerative neuropathy||CA||[63–66]|||
|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.||||[76, 77]|
|SCP2||SCPx||Fertility abnormalities. Brain lesions with motor disorders||Phytanic acid-restricted diet||[78, 79]|||
|SLC27A5||BACS||No signs of liver disease||N.D.||||[82, 83]|
|BAAT||BAAT||Neonatal cholestasis. Malabsorption of fat-soluble vitamins. Rickets||GCA||[84, 86]|||
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
REE, EH, ASM and PSS played a main role in collecting information; JJGM coordinated the study; MJM wrote the first draft.
The authors declare that they have no conflicts of interest.
This study was funded by the CIBERehd (EHD15PI05/2016) and “Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III”, Spain (PI19/00819 and PI20/00189, co-funded by European Regional Development Fund/European Social Fund, “Investing in your future”); “Junta de Castilla y Leon” (SA074P20); Fundació Marato TV3 (Ref. 201916-31), Spain; AECC Scientific Foundation (2017/2020), Spain; “Centro Internacional sobre el Envejecimiento” (OLD-HEPAMARKER, 0348_CIE_6_E), Spain. REE was supported by a predoctoral contract funded by “Junta de Castilla y Leon” and “Fondo Social Europeo” (EDU/574/2018). ASM and PSS are supported by a predoctoral scholarship (FPU) funded by the Ministry of Science, Innovation and Universities, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
© The Author(s) 2022.