*3.2. Congenital Bile Acid Synthesis Defect Type 5*

Although mutations were found in the ABCD3 gene of a Zellweger patient [64], further evidence showed that ABCD3 has no link with peroxisomal biogenesis and is definitively not associated with Zellweger Syndrome [95]. ABCD3, which presents partial functional redundancy with ABCD1, has been shown to transport branched-chain FAs, dicarboxylic acids, and bile acid precursors. A few years ago, the accumulation of peroxisomal C27-bile acid intermediates DHCA and THCA, as well as VLCFAs, was described in a young Turkish girl whose parents were consanguineous [67]. The patient presented hepatosplenomegaly and a severe progressive liver disease and she died of complications after liver transplantation. Patient fibroblasts showed reduced numbers of enlarged peroxisomes, as well as reduced β-oxidation of pristanic acid, compared to controls. Immunofluorescence confirmed the absence of ABCD3 in the peroxisomal membrane. A homozygous truncating mutation was identified in the ABCD3 gene of the patient, and the disease was named congenital bile acid synthesis defect (CBAS) type 5 (OMIM # 616278). It should be noted that CBAS type 1, 2, 3, 4, and 6 are associated with mutations in HSD3B7, AKR1D1, CYP7B1, AMACR, and ACOX2 respectively. These genes control key reactions in bile acid synthesis and all the CBAS forms present an autosomal recessive inheritance.
