AKR1D1 and CYP7B1 mutations in patients with inborn errors of bile acid metabolism: Possibly underdiagnosed diseases
Background: Inborn errors of bile acid metabolism (IEBAM) cause rare but treatable genetic disorders that can present as neonatal cholestasis or neurological diseases. Without timely primary bile acid treatment, patients may develop liver failure early in life. This study aimed to analyze the types...
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Elsevier
2020-02-01
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| Series: | Pediatrics and Neonatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1875957219300956 |
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| author | Ju-Yin Chen Jia-Feng Wu Akihiko Kimura Hiroshi Nittono Bang-Yu Liou Chee-Seng Lee Ho-Sheng Chen Yu-Chun Chiu Yen-Hsuan Ni Steven Shinn-Forng Peng Wang-Tso Lee I-Jung Tsai Mei-Hwei Chang Huey-Ling Chen |
| author_facet | Ju-Yin Chen Jia-Feng Wu Akihiko Kimura Hiroshi Nittono Bang-Yu Liou Chee-Seng Lee Ho-Sheng Chen Yu-Chun Chiu Yen-Hsuan Ni Steven Shinn-Forng Peng Wang-Tso Lee I-Jung Tsai Mei-Hwei Chang Huey-Ling Chen |
| author_sort | Ju-Yin Chen |
| collection | DOAJ |
| description | Background: Inborn errors of bile acid metabolism (IEBAM) cause rare but treatable genetic disorders that can present as neonatal cholestasis or neurological diseases. Without timely primary bile acid treatment, patients may develop liver failure early in life. This study aimed to analyze the types and treatment outcomes of IEBAM in Taiwanese infants and document the allele frequency of CYP7B1 hot spot mutations in the population. Methods: Urine samples from patients with infantile intrahepatic cholestasis and suspected IEBAM were subjected to urinary bile acid analysis by gas chromatography-mass spectrometry (GC/MS). Genetic diagnoses were made using direct sequencing or next-generation sequencing. We also tested healthy control subjects for a probable hot spot point mutation of CYP7B1. Results: Among the 75 patients with infantile intrahepatic cholestasis tested during 2000 –2016, three had ∆4-3-oxosteroid 5β-reductase deficiency with AKR1D1 mutations, and three had oxysterol-7α-hydroxylase deficiency with CYP7B1 mutation. Two patients with ∆4-3-oxosteroid 5β-reductase deficiency were successfully treated with cholic acid. The three unrelated infants with oxysterol 7α-hydroxylase deficiencies had the same p.R112X homozygous CYP7B1 mutation. Two had mild renal or neurological involvement. Among 608 healthy control subjects, the allele frequency of the heterozygous mutation for p.R112X was 2/1216 (0.16%). The only surviving patient with oxysterol 7α-hydroxylase deficiency recovered from liver failure after chenodeoxycholic acid (CDCA) treatment beginning at 3 months of age. Conclusion: Distinct types of IEBAM disease were found in the Taiwanese population. Patients with early diagnosis and early treatment had a favorable outcome. IEBAM prevalence rates may be higher than expected due to the presence of heterozygous mutations in the general population. Key Words: chenodeoxycholic acid, cholic acid, inborn errors of bile acid metabolism, neonatal cholestasis, oxysterol 7α-hydroxylase deficiency |
| format | Article |
| id | doaj-art-bc23a19a3e6d4a19a24bb123280ed82d |
| institution | OA Journals |
| issn | 1875-9572 |
| language | English |
| publishDate | 2020-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pediatrics and Neonatology |
| spelling | doaj-art-bc23a19a3e6d4a19a24bb123280ed82d2025-08-20T02:00:43ZengElsevierPediatrics and Neonatology1875-95722020-02-01611758310.1016/j.pedneo.2019.06.009AKR1D1 and CYP7B1 mutations in patients with inborn errors of bile acid metabolism: Possibly underdiagnosed diseasesJu-Yin Chen0Jia-Feng Wu1Akihiko Kimura2Hiroshi Nittono3Bang-Yu Liou4Chee-Seng Lee5Ho-Sheng Chen6Yu-Chun Chiu7Yen-Hsuan Ni8Steven Shinn-Forng Peng9Wang-Tso Lee10I-Jung Tsai11Mei-Hwei Chang12Huey-Ling Chen13Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital Yunlin Branch, Yunlin, TaiwanDepartment of Pediatrics, National Taiwan University Hospital, Taipei, TaiwanDepartment of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, JapanJunshin Clinic Bile Acid Institute, Meguro-ku, Tokyo, JapanHepatitis Research Centre, National Taiwan University Hospital, Taipei, TaiwanDepartment of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, TaiwanDepartment of Pediatrics, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, TaiwanDepartment of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Education, National Taiwan University Hospital, Taipei, TaiwanDepartment of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Centre, National Taiwan University Hospital, Taipei, TaiwanDepartment of Radiology, National Taiwan University Hospital, Taipei, TaiwanDepartment of Pediatrics, National Taiwan University Hospital, Taipei, TaiwanDepartment of Pediatrics, National Taiwan University Hospital, Taipei, TaiwanDepartment of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Centre, National Taiwan University Hospital, Taipei, TaiwanDepartment of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Centre, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Education and Bioethics, Graduate Institute of Medical Education and Bioethics, National Taiwan University College of Medicine, Taipei, Taiwan; Corresponding author. Department of Pediatrics, Department of Medical Education and Bioethics, National Taiwan University College of Medicine and Hospital, 17F, No. 8, Chung Shan S. Rd, Taipei, 100, Taiwan.Background: Inborn errors of bile acid metabolism (IEBAM) cause rare but treatable genetic disorders that can present as neonatal cholestasis or neurological diseases. Without timely primary bile acid treatment, patients may develop liver failure early in life. This study aimed to analyze the types and treatment outcomes of IEBAM in Taiwanese infants and document the allele frequency of CYP7B1 hot spot mutations in the population. Methods: Urine samples from patients with infantile intrahepatic cholestasis and suspected IEBAM were subjected to urinary bile acid analysis by gas chromatography-mass spectrometry (GC/MS). Genetic diagnoses were made using direct sequencing or next-generation sequencing. We also tested healthy control subjects for a probable hot spot point mutation of CYP7B1. Results: Among the 75 patients with infantile intrahepatic cholestasis tested during 2000 –2016, three had ∆4-3-oxosteroid 5β-reductase deficiency with AKR1D1 mutations, and three had oxysterol-7α-hydroxylase deficiency with CYP7B1 mutation. Two patients with ∆4-3-oxosteroid 5β-reductase deficiency were successfully treated with cholic acid. The three unrelated infants with oxysterol 7α-hydroxylase deficiencies had the same p.R112X homozygous CYP7B1 mutation. Two had mild renal or neurological involvement. Among 608 healthy control subjects, the allele frequency of the heterozygous mutation for p.R112X was 2/1216 (0.16%). The only surviving patient with oxysterol 7α-hydroxylase deficiency recovered from liver failure after chenodeoxycholic acid (CDCA) treatment beginning at 3 months of age. Conclusion: Distinct types of IEBAM disease were found in the Taiwanese population. Patients with early diagnosis and early treatment had a favorable outcome. IEBAM prevalence rates may be higher than expected due to the presence of heterozygous mutations in the general population. Key Words: chenodeoxycholic acid, cholic acid, inborn errors of bile acid metabolism, neonatal cholestasis, oxysterol 7α-hydroxylase deficiencyhttp://www.sciencedirect.com/science/article/pii/S1875957219300956 |
| spellingShingle | Ju-Yin Chen Jia-Feng Wu Akihiko Kimura Hiroshi Nittono Bang-Yu Liou Chee-Seng Lee Ho-Sheng Chen Yu-Chun Chiu Yen-Hsuan Ni Steven Shinn-Forng Peng Wang-Tso Lee I-Jung Tsai Mei-Hwei Chang Huey-Ling Chen AKR1D1 and CYP7B1 mutations in patients with inborn errors of bile acid metabolism: Possibly underdiagnosed diseases Pediatrics and Neonatology |
| title | AKR1D1 and CYP7B1 mutations in patients with inborn errors of bile acid metabolism: Possibly underdiagnosed diseases |
| title_full | AKR1D1 and CYP7B1 mutations in patients with inborn errors of bile acid metabolism: Possibly underdiagnosed diseases |
| title_fullStr | AKR1D1 and CYP7B1 mutations in patients with inborn errors of bile acid metabolism: Possibly underdiagnosed diseases |
| title_full_unstemmed | AKR1D1 and CYP7B1 mutations in patients with inborn errors of bile acid metabolism: Possibly underdiagnosed diseases |
| title_short | AKR1D1 and CYP7B1 mutations in patients with inborn errors of bile acid metabolism: Possibly underdiagnosed diseases |
| title_sort | akr1d1 and cyp7b1 mutations in patients with inborn errors of bile acid metabolism possibly underdiagnosed diseases |
| url | http://www.sciencedirect.com/science/article/pii/S1875957219300956 |
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