Primary systemic carnitine deficiency: Phenotypic variability, diagnostic challenges, and long-term outcomes.

IF 0.9 4区 医学 Q3 PEDIATRICS
Eymen Pınar, Tanyel Zubarioglu, Hanım Babazade, Kağan Çalışgan, Mehmet Şerif Cansever, Ertuğrul Kıykım, Çiğdem Aktuğlu Zeybek
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Abstract

Background: Primary systemic carnitine deficiency (CDSP) is a rare inherited metabolic disorder characterized by impaired carnitine transport due to mutations in the SLC22A5 gene, leading to impaired mitochondrial fatty acid oxidation. The aim of this retrospective, descriptive study was to investigate the clinical, biochemical, and molecular features of CDSP in Turkey, where the lack of a national expanded metabolic screening program contributes to delayed diagnosis and severe complications.

Methods: The clinical, biochemical, and molecular profiles of 12 patients from eight families diagnosed between 2003 and 2025 were retrospectively analyzed. Data on family history, consanguinity, clinical manifestations-including cardiomyopathy, muscle weakness, neurological symptoms, and liver dysfunction-plasma free carnitine levels, and echocardiographic measurements were collected and analyzed.

Results: The majority of patients (92%) were from consanguineous families. Cardiomyopathy was the most common clinical feature (75%), followed by muscle weakness (50%), neurological symptoms (42%), and liver dysfunction (33%). A novel SLC22A5 variant (c.125T>C; p.Leu42Pro) was identified that expands the known genetic spectrum of CDSP. Oral carnitine supplementation significantly increased plasma free carnitine levels (p = 0.01) and improved long-term interventricular septal thickness Z-scores (p = 0.045). In addition, cholestasis was observed in two patients, suggesting an expanded disease phenotype.

Conclusion: These results emphasize the crucial role of early detection and family screening in the prevention of life-threatening complications associated with CDSP. Long-term carnitine therapy improves metabolic and cardiac outcomes, underscoring the need for early intervention and inclusion of CDSP in national newborn screening programs.

原发性系统性肉碱缺乏症:表型变异、诊断挑战和长期结果。
背景:原发性系统性肉毒碱缺乏症(CDSP)是一种罕见的遗传性代谢疾病,其特征是由于SLC22A5基因突变导致肉毒碱运输受损,导致线粒体脂肪酸氧化受损。这项回顾性描述性研究的目的是调查土耳其CDSP的临床、生化和分子特征,土耳其缺乏全国性的扩大代谢筛查计划,导致诊断延迟和严重并发症。方法:回顾性分析2003 ~ 2025年间确诊的8个家族12例患者的临床、生化和分子特征。收集和分析家族史、血亲关系、临床表现(包括心肌病、肌肉无力、神经系统症状和肝功能障碍)、血浆游离肉碱水平和超声心动图测量数据。结果:绝大多数患者(92%)来自近亲家庭。心肌病是最常见的临床特征(75%),其次是肌肉无力(50%)、神经症状(42%)和肝功能障碍(33%)。一种新的SLC22A5变异(C . 125t >C; p.Leu42Pro)被鉴定出来,扩展了已知的CDSP遗传谱。口服肉碱可显著提高血浆游离肉碱水平(p = 0.01),改善长期室间隔厚度z评分(p = 0.045)。此外,在两名患者中观察到胆汁淤积,提示疾病表型扩大。结论:这些结果强调了早期发现和家庭筛查在预防与CDSP相关的危及生命的并发症中的重要作用。长期肉碱治疗可改善代谢和心脏预后,强调早期干预和将CDSP纳入国家新生儿筛查计划的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Pediatrics International
Pediatrics International 医学-小儿科
CiteScore
2.00
自引率
7.10%
发文量
519
审稿时长
12 months
期刊介绍: Publishing articles of scientific excellence in pediatrics and child health delivery, Pediatrics International aims to encourage those involved in the research, practice and delivery of child health to share their experiences, ideas and achievements. Formerly Acta Paediatrica Japonica, the change in name in 1999 to Pediatrics International, reflects the Journal''s international status both in readership and contributions (approximately 45% of articles published are from non-Japanese authors). The Editors continue their strong commitment to the sharing of scientific information for the benefit of children everywhere. Pediatrics International opens the door to all authors throughout the world. Manuscripts are judged by two experts solely upon the basis of their contribution of original data, original ideas and their presentation.
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