Current Understanding of Pathogenic Mechanisms and Disease Models of Citrin Deficiency
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| Formato: | Artículo Open Access |
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Wiley
2025
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| _version_ | 1867010931973685248 |
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| author | Denis Lacabanne Alice P. Sowton Bosco Jose Edmund R. S. Kunji Sotiria Tavoulari |
| author_facet | Denis Lacabanne Alice P. Sowton Bosco Jose Edmund R. S. Kunji Sotiria Tavoulari Denis Lacabanne Alice P. Sowton Bosco Jose Edmund R. S. Kunji Sotiria Tavoulari |
| collection | Wiley Open Access |
| contents | Current Understanding of Pathogenic Mechanisms and Disease Models of Citrin Deficiency Denis Lacabanne Alice P. Sowton Bosco Jose Edmund R. S. Kunji Sotiria Tavoulari Journal of Inherited Metabolic Disease ABSTRACT Citrin deficiency (CD) is a complex mitochondrial disease with three different age‐related stages: neonatal intrahepatic cholestasis caused by CD (NICCD), failure to thrive and dyslipidemia caused by CD (FTTDCD), and type II citrullinemia (CTLN2), recently renamed adolescent and adult CD (AACD). While highly prevalent in the Asian population, CD is pan‐ethnic and remains severely underdiagnosed. The disease is caused by the dysfunction or absence of the mitochondrial aspartate/glutamate carrier 2 (AGC2/SLC25A13), also known as citrin. Citrin deficiency results in a direct impairment of the malate–aspartate shuttle and the urea cycle, with expected knock‐on effects on a multitude of other metabolic pathways, leading to a complicated pathophysiology. Here, we discuss our current knowledge of the molecular mechanism of substrate transport by citrin, including recent advances suggesting against its calcium regulation. We also discuss the different types of pathogenic variants found in CD patients and new insights into their pathogenic mechanisms. Additionally, we provide a summary and assessment of the efforts to develop preclinical models as well as treatments for the disease. 10.1002/jimd.70021 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/jimd.70021 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_jimd_70021 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Current Understanding of Pathogenic Mechanisms and Disease Models of Citrin Deficiency Denis Lacabanne Alice P. Sowton Bosco Jose Edmund R. S. Kunji Sotiria Tavoulari Journal of Inherited Metabolic Disease Current Understanding of Pathogenic Mechanisms and Disease Models of Citrin Deficiency Denis Lacabanne Alice P. Sowton Bosco Jose Edmund R. S. Kunji Sotiria Tavoulari Journal of Inherited Metabolic Disease ABSTRACT Citrin deficiency (CD) is a complex mitochondrial disease with three different age‐related stages: neonatal intrahepatic cholestasis caused by CD (NICCD), failure to thrive and dyslipidemia caused by CD (FTTDCD), and type II citrullinemia (CTLN2), recently renamed adolescent and adult CD (AACD). While highly prevalent in the Asian population, CD is pan‐ethnic and remains severely underdiagnosed. The disease is caused by the dysfunction or absence of the mitochondrial aspartate/glutamate carrier 2 (AGC2/SLC25A13), also known as citrin. Citrin deficiency results in a direct impairment of the malate–aspartate shuttle and the urea cycle, with expected knock‐on effects on a multitude of other metabolic pathways, leading to a complicated pathophysiology. Here, we discuss our current knowledge of the molecular mechanism of substrate transport by citrin, including recent advances suggesting against its calcium regulation. We also discuss the different types of pathogenic variants found in CD patients and new insights into their pathogenic mechanisms. Additionally, we provide a summary and assessment of the efforts to develop preclinical models as well as treatments for the disease. 10.1002/jimd.70021 http://creativecommons.org/licenses/by/4.0/ |
| title | Current Understanding of Pathogenic Mechanisms and Disease Models of Citrin Deficiency |
| topic | Journal of Inherited Metabolic Disease |
| url | https://onlinelibrary.wiley.com/doi/10.1002/jimd.70021 |