Platek, Teresa and Orso, Evelyn and Zapala, Barbara and Polus, Anna and Kiec-Wilk, Beata and Piwowar, Monika and Chojnacka, Monika and Cialowicz, Urszula and Malczewska-Malec, Malgorzata and Schmitz, Gerd and Solnica, Bogdan and Dembinska-Kiec, Aldona (2018) Case report of dysregulation of primary bile acid synthesis in a family with X-linked adrenoleukodystrophy. MEDICINE, 97 (49): e13353. ISSN 0025-7974, 1536-5964
Full text not available from this repository. (Request a copy)Abstract
Rationale: X-linked adrenoleukodystrophy (X-ALD) is a rare disorder caused by mutations in the ABCD1 gene, coding for peroxisomal membrane transporter adrenoleukodystrophy (ALD) protein. The disease is characterized by accumulation of very long chain fatty acids (VLCFAs) in tissues. Adult adrenomyeloneuropathy (AMN) and the cerebral inflammatory form of ALD are the main phenotypes presenting various symptoms. Patient concerns: We report a case of 37-year-old patient with diagnosis of X-ALD, confirmed based on elevated VLCFA concentrations and genetic testing of ABCD1 gene. The complete clinical picture in the patient indicates AMN phenotype with cerebral involvement. Diagnoses: The reduced synthesis of unconjugated cholic and chenodeoxycholic acids, and the reduction to 28% to 29% of peroxisomal beta-oxidation of behenic acid and normal peroxisomal metabolism of pristanic and palmitic acid were observed in the X-ALD patient. Sanger sequencing of major genes involved in primary bile acid (BA) synthesis failed to identify pathogenic mutations of the investigated set of genes. Interventions: Plasma concentrations of BAs, VLCFAs, and beta-oxidation of C22:0, C16:0, and pristanic acid were studied in primary skin fibroblasts of the patient. In addition, we performed sequencing of the ABCD1, ABCD3, CYP7A1, CYP7B1, CYP27A1, HSD3B7, AKR1D1, and SLC27A5 genes in the X-ALD family. Outcomes: In the Polish family affected with AMN a dysregulation of the primary BA synthesis pathway was found. Lessons: We have demonstrated the coincidence of the adult form of X-ALD with abnormalities in BA synthesis. We suggest that decreased synthesis of BAs may be an additional dysfunction as a consequence of the ABCD1 c.659T>C, p.(Leu220Pro) mutation and may be further evidence that disturbed cholesterol metabolism is important in the pathology of ALD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHAIN FATTY-ACIDS; IDENTIFICATION; BIOSYNTHESIS; FIBROBLASTS; MUTATIONS; TRANSPORT; SPECTRUM; PLASMA; STATE; ALD; ABCD1 gene; bile acids; peroxisomal beta-oxidation; X-linked adrenoleukodystrophy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Oct 2019 08:21 |
| Last Modified: | 04 Oct 2019 08:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13390 |
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