{"title":"The status of adult patients with citrin deficiency in Japan: A report from the nation-wide study","authors":"Jun Kido , Johannes Häberle , Keishin Sugawara , Masahide Yazaki , Ayano Inui , Chikahiko Numakura , Masaru Shimura , Keinosuke Ishido , Naomi Kuranobu , Kenyu Hashimoto , Kimitoshi Nakamura","doi":"10.1016/j.ymgme.2025.109221","DOIUrl":null,"url":null,"abstract":"<div><div>Citrin deficiency is an autosomal recessive disorder caused by mutations in <em>SLC25A13</em>, encoding the inner mitochondrial membrane protein citrin. This disease manifests in age-dependent forms: neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), failure to thrive and dyslipidemia caused by citrin deficiency, and adolescent and adult citrin deficiency (AACD). While NICCD often resolves with early treatment, AACD symptoms tend to persist or worsen over time. However, the long-term outcome in adult patients with citrin deficiency, particularly those affected by the symptoms of AACD, is not well understood. To address this gap, we conducted a new study from 2022 to 2024 that focused specifically on adult patients with citrin deficiency.</div><div>This retrospective study investigated the long-term outcomes in a total of 128 adult patients, categorized depending on their onset of disease into NICCD, Post-NICCD, and AACD groups. Significant differences in height were observed: NICCD patients had taller median heights than AACD patients (Males: 170.6 cm vs. 168.0 cm, <em>P</em> = 0.016; Females: 156.0 cm vs. 153.0 cm, <em>P</em> = 0.007). Former NICCD patients generally achieved favorable long-term outcomes with early intervention, while AACD patients often experienced persistent or worsening symptoms, including irreversible liver damage with impaired urea cycle function.</div><div>In conclusion, this study suggests that early intervention during infancy or childhood may improve long-term prognosis in citrin deficiency, particularly for NICCD patients. Conversely, outcome for AACD patients remains a concern, highlighting the need for improved management strategies in adulthood. This study emphasizes the importance of timely diagnosis and treatment to mitigate the progressive nature of citrin deficiency.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"146 1","pages":"Article 109221"},"PeriodicalIF":3.5000,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular genetics and metabolism","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1096719225002124","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Citrin deficiency is an autosomal recessive disorder caused by mutations in SLC25A13, encoding the inner mitochondrial membrane protein citrin. This disease manifests in age-dependent forms: neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), failure to thrive and dyslipidemia caused by citrin deficiency, and adolescent and adult citrin deficiency (AACD). While NICCD often resolves with early treatment, AACD symptoms tend to persist or worsen over time. However, the long-term outcome in adult patients with citrin deficiency, particularly those affected by the symptoms of AACD, is not well understood. To address this gap, we conducted a new study from 2022 to 2024 that focused specifically on adult patients with citrin deficiency.
This retrospective study investigated the long-term outcomes in a total of 128 adult patients, categorized depending on their onset of disease into NICCD, Post-NICCD, and AACD groups. Significant differences in height were observed: NICCD patients had taller median heights than AACD patients (Males: 170.6 cm vs. 168.0 cm, P = 0.016; Females: 156.0 cm vs. 153.0 cm, P = 0.007). Former NICCD patients generally achieved favorable long-term outcomes with early intervention, while AACD patients often experienced persistent or worsening symptoms, including irreversible liver damage with impaired urea cycle function.
In conclusion, this study suggests that early intervention during infancy or childhood may improve long-term prognosis in citrin deficiency, particularly for NICCD patients. Conversely, outcome for AACD patients remains a concern, highlighting the need for improved management strategies in adulthood. This study emphasizes the importance of timely diagnosis and treatment to mitigate the progressive nature of citrin deficiency.
Citrin缺乏症是一种常染色体隐性遗传病,由编码线粒体内膜蛋白Citrin的SLC25A13突变引起。这种疾病表现为年龄依赖性形式:由柠檬素缺乏引起的新生儿肝内胆汁淤积症(NICCD),由柠檬素缺乏引起的发育不良和血脂异常,以及青少年和成人柠檬素缺乏(AACD)。虽然NICCD通常通过早期治疗得以解决,但AACD症状往往会持续存在或随着时间的推移而恶化。然而,成年柠檬素缺乏症患者的长期预后,特别是受AACD症状影响的患者,尚不清楚。为了解决这一差距,我们从2022年到2024年进行了一项新的研究,专门针对柑橘素缺乏症的成年患者。这项回顾性研究调查了128名成年患者的长期结果,根据他们的发病分为NICCD、NICCD后和AACD组。身高差异有统计学意义:NICCD患者的中位身高高于AACD患者(男性:170.6 cm比168.0 cm, P = 0.016;女性:156.0 cm比153.0 cm, P = 0.007)。前NICCD患者通常通过早期干预获得良好的长期预后,而AACD患者通常经历持续或恶化的症状,包括尿素循环功能受损的不可逆肝损伤。总之,本研究提示婴儿期或儿童期早期干预可能改善柠檬素缺乏症的长期预后,特别是NICCD患者。相反,AACD患者的预后仍然令人担忧,强调需要改善成年期的管理策略。本研究强调及时诊断和治疗的重要性,以减轻柠檬素缺乏症的进行性。
期刊介绍:
Molecular Genetics and Metabolism contributes to the understanding of the metabolic and molecular basis of disease. This peer reviewed journal publishes articles describing investigations that use the tools of biochemical genetics and molecular genetics for studies of normal and disease states in humans and animal models.