Keser Merve, Demirci Büşra, Uçar Habibe Koç, Akgün Özlem, Arslan İlknur, Gürbüz Berrak Bilginer
Division of Pediatrics, Ankara Bilkent City Hospital, Ankara, Turkey.
Division of Pediatric Neurology, Adana City Hospital, Adana, Turkey.
Mol Syndromol. 2025 Apr 1:1-7. doi: 10.1159/000545585.
Mitochondrial DNA depletion syndromes encompass rare genetic disorders stemming from various gene defects, including encephalomyopathic mtDNA depletion syndrome 13 (MTDPS13), an autosomal recessive condition linked to gene variants. Although its prevalence is estimated at 1/100,000-400,000, the mechanism behind MTDPS13 remains incompletely understood. Recent studies suggest variants disrupt mitophagy, contributing to its pathogenesis.
A 3-year and 4-month-old male presented with respiratory distress, diarrhea, and unconsciousness. His medical history revealed developmental delay and dysmorphic features. Physical examination unveiled characteristic dysmorphisms, while neurological assessment indicated abnormalities. Laboratory findings exhibited metabolic disturbances consistent with MTDPS13, confirmed by genetic analysis revealing a homozygous c.1555C>T variant.
FBXL4 defects, found in approximately 0.7% of suspected mitochondrial disease cases, lead to varied phenotypes with nonspecific facial dysmorphisms. The patient's presentation aligned with reported features, including growth delay, hypotonia, and developmental delay. Notably, the diagnosis occurred later than typical onset, highlighting the variability in disease manifestation. Treatment focused on symptom management, with dichloroacetic acid effectively addressing lactic acidosis. This case underscores the importance of considering mitochondrial diseases, particularly FBXL4-related MTDPS13, in patients presenting with metabolic disturbances and dysmorphic features. Early recognition facilitates appropriate management and genetic counseling for affected families.
线粒体DNA耗竭综合征包括由各种基因缺陷引起的罕见遗传疾病，其中包括脑肌病性线粒体DNA耗竭综合征13（MTDPS13），这是一种与基因变异相关的常染色体隐性疾病。尽管其患病率估计为1/100,000 - 400,000，但MTDPS13背后的机制仍未完全了解。最近的研究表明，这些变异会破坏线粒体自噬，从而促进其发病机制。
一名3岁4个月大的男性出现呼吸窘迫、腹泻和昏迷。他的病史显示有发育迟缓及畸形特征。体格检查发现了特征性畸形，而神经学评估显示存在异常。实验室检查结果显示出与MTDPS13一致的代谢紊乱，基因分析证实存在纯合子c.1555C>T变异。
在大约0.7%的疑似线粒体疾病病例中发现的FBXL4缺陷会导致具有非特异性面部畸形的多种表型。患者的表现与报道的特征相符，包括生长发育迟缓、肌张力减退和发育迟缓。值得注意 的是，诊断时间晚于典型发病时间，突出了疾病表现的变异性。治疗重点是症状管理，二氯乙酸有效解决了乳酸酸中毒问题。该病例强调了在出现代谢紊乱和畸形特征 的患者中考虑线粒体疾病，特别是与FBXL4相关的MTDPS13的重要性。早期识别有助于对受影响家庭进行适当的管理和遗传咨询。
