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Clinical and genetic features of congenital bile acid synthesis defect with a novel mutation in AKR1D1 gene sequencing: Case reports
RATIONALE: Congenital bile acid synthesis defect (BASD) is a rare disease caused by mutations in the aldo-keto reductase 1D1 gene, which encodes the primary Δ4-3-oxosteroid 5β-reductase enzyme. Early disease diagnosis is critical for early treatment with bile acid replacement therapy, with an excell...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276355/ https://www.ncbi.nlm.nih.gov/pubmed/35758383 http://dx.doi.org/10.1097/MD.0000000000029476 |
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author | Pham, Anh-Hoa Nguyen Thi, Kim-Oanh Bui Thi, Mai-Huong Nguyen Ngo, Diem-Ngoc Naritaka, Nakayuki Nittono, Hiroshi Hayashi, Hisamitsu Dao, Trang Thi Nguyen, Kim-Huong Thi Nguyen, Hoai-Nghia Giang, Hoa Tang, Hung-Sang Nguyen, Tat-Thanh Truong, Dinh-Kiet Tran, Minh-Dien |
author_facet | Pham, Anh-Hoa Nguyen Thi, Kim-Oanh Bui Thi, Mai-Huong Nguyen Ngo, Diem-Ngoc Naritaka, Nakayuki Nittono, Hiroshi Hayashi, Hisamitsu Dao, Trang Thi Nguyen, Kim-Huong Thi Nguyen, Hoai-Nghia Giang, Hoa Tang, Hung-Sang Nguyen, Tat-Thanh Truong, Dinh-Kiet Tran, Minh-Dien |
author_sort | Pham, Anh-Hoa Nguyen |
collection | PubMed |
description | RATIONALE: Congenital bile acid synthesis defect (BASD) is a rare disease caused by mutations in the aldo-keto reductase 1D1 gene, which encodes the primary Δ4-3-oxosteroid 5β-reductase enzyme. Early disease diagnosis is critical for early treatment with bile acid replacement therapy, with an excellent chance for recovery. In contrast, protracted diagnosis and treatment may lead to poor outcomes, including decompensated hepatic cirrhosis, liver transplant, and even death. PATIENT CONCERNS: Three clinical congenital bile acid synthesis defect cases in the Vietnamese population are herein reported. These pediatric patients presented with symptoms of prolonged postpartum jaundice and abnormal loose stool (mucus, lipids, and white). The clinical examinations showed hepatosplenomegaly. Urinalysis showed a very low fraction of primary bile acids and atypical 3-oxo-Δ4- bile acids in all three patients. DIAGNOSES: The patients were diagnosed with primary Δ4-3-oxosteroid 5β-reductase deficiency. Next-generation gene sequencing revealed two homozygous mutations in the aldo-keto reductase family 1 member D1 gene. The first is a documented variant, c.797G>A (p.Arg266Gln), and the second is a novel mutation at c.155T>C (p.Ile52Thr). INTERVENTIONS: Immediately after diagnosis, patients were treated with oral chenodeoxycholate 5 mg/kg/d. OUTCOMES: The patients’ symptoms, signs, and primary bile acids levels improved significantly. LESSONS: Clinicians should consider genetic disorders related to cholestasis for effective and life-saving treatment. A prompt genetic analysis by next-generation gene sequencing enables patients to access bile acid replacement therapy earlier, significantly improving short- and long-term outcomes. |
format | Online Article Text |
id | pubmed-9276355 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-92763552022-07-13 Clinical and genetic features of congenital bile acid synthesis defect with a novel mutation in AKR1D1 gene sequencing: Case reports Pham, Anh-Hoa Nguyen Thi, Kim-Oanh Bui Thi, Mai-Huong Nguyen Ngo, Diem-Ngoc Naritaka, Nakayuki Nittono, Hiroshi Hayashi, Hisamitsu Dao, Trang Thi Nguyen, Kim-Huong Thi Nguyen, Hoai-Nghia Giang, Hoa Tang, Hung-Sang Nguyen, Tat-Thanh Truong, Dinh-Kiet Tran, Minh-Dien Medicine (Baltimore) 6200 RATIONALE: Congenital bile acid synthesis defect (BASD) is a rare disease caused by mutations in the aldo-keto reductase 1D1 gene, which encodes the primary Δ4-3-oxosteroid 5β-reductase enzyme. Early disease diagnosis is critical for early treatment with bile acid replacement therapy, with an excellent chance for recovery. In contrast, protracted diagnosis and treatment may lead to poor outcomes, including decompensated hepatic cirrhosis, liver transplant, and even death. PATIENT CONCERNS: Three clinical congenital bile acid synthesis defect cases in the Vietnamese population are herein reported. These pediatric patients presented with symptoms of prolonged postpartum jaundice and abnormal loose stool (mucus, lipids, and white). The clinical examinations showed hepatosplenomegaly. Urinalysis showed a very low fraction of primary bile acids and atypical 3-oxo-Δ4- bile acids in all three patients. DIAGNOSES: The patients were diagnosed with primary Δ4-3-oxosteroid 5β-reductase deficiency. Next-generation gene sequencing revealed two homozygous mutations in the aldo-keto reductase family 1 member D1 gene. The first is a documented variant, c.797G>A (p.Arg266Gln), and the second is a novel mutation at c.155T>C (p.Ile52Thr). INTERVENTIONS: Immediately after diagnosis, patients were treated with oral chenodeoxycholate 5 mg/kg/d. OUTCOMES: The patients’ symptoms, signs, and primary bile acids levels improved significantly. LESSONS: Clinicians should consider genetic disorders related to cholestasis for effective and life-saving treatment. A prompt genetic analysis by next-generation gene sequencing enables patients to access bile acid replacement therapy earlier, significantly improving short- and long-term outcomes. Lippincott Williams & Wilkins 2022-06-24 /pmc/articles/PMC9276355/ /pubmed/35758383 http://dx.doi.org/10.1097/MD.0000000000029476 Text en Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) |
spellingShingle | 6200 Pham, Anh-Hoa Nguyen Thi, Kim-Oanh Bui Thi, Mai-Huong Nguyen Ngo, Diem-Ngoc Naritaka, Nakayuki Nittono, Hiroshi Hayashi, Hisamitsu Dao, Trang Thi Nguyen, Kim-Huong Thi Nguyen, Hoai-Nghia Giang, Hoa Tang, Hung-Sang Nguyen, Tat-Thanh Truong, Dinh-Kiet Tran, Minh-Dien Clinical and genetic features of congenital bile acid synthesis defect with a novel mutation in AKR1D1 gene sequencing: Case reports |
title | Clinical and genetic features of congenital bile acid synthesis defect with a novel mutation in AKR1D1 gene sequencing: Case reports |
title_full | Clinical and genetic features of congenital bile acid synthesis defect with a novel mutation in AKR1D1 gene sequencing: Case reports |
title_fullStr | Clinical and genetic features of congenital bile acid synthesis defect with a novel mutation in AKR1D1 gene sequencing: Case reports |
title_full_unstemmed | Clinical and genetic features of congenital bile acid synthesis defect with a novel mutation in AKR1D1 gene sequencing: Case reports |
title_short | Clinical and genetic features of congenital bile acid synthesis defect with a novel mutation in AKR1D1 gene sequencing: Case reports |
title_sort | clinical and genetic features of congenital bile acid synthesis defect with a novel mutation in akr1d1 gene sequencing: case reports |
topic | 6200 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276355/ https://www.ncbi.nlm.nih.gov/pubmed/35758383 http://dx.doi.org/10.1097/MD.0000000000029476 |
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