Pediatrics Department, Centro Materno Infantil do Norte, Centro Hospitalar do Porto, Largo da Maternidade, S/N, 4450, Porto, Portugal.
Reference Center for Inherited Metabolic Disorders, Centro Hospitalar do Porto, Porto, Portugal.
Eur J Pediatr. 2019 Jan;178(1):21-32. doi: 10.1007/s00431-018-3292-x. Epub 2018 Dec 7.
Primary mitochondrial disorders are highly variable in clinical presentation, biochemistry, and molecular etiology. Mitochondrial disorders can be caused by genetic defects in the mitochondrial, in nuclear genome, or in the interplay between the two genomes. Biochemical screening tests may be inconclusive or misleading since patients, with confirmed mitochondrial disorders specially in pediatric age, may exhibit normal routine biochemistry, muscle histology, or enzymatic analysis of the mitochondrial respiratory chain. Diagnosis is often challenging even with combination of multiple criteria (clinical, biochemical, histological, and functional), as innumerous conditions cause secondary mitochondrial dysfunction. Nowadays, a definite diagnosis is only possible by genetic confirmation since no single score system is satisfactorily accurate, being sensitive but not specific.Conclusion: Awareness between physicians is of major importance considering that clinical suspicion may not be obvious regarding the heterogenicity in presentation and biochemical features of mitochondrial disorders. In this review, we provide information on diagnosis approach to patients suspected for mitochondrial disorders as well as management on chronic and acute settings. Follow-up should provide comprehensive information on patient's status, since intervention on these diseases is mostly supportive and prognosis is variable and sometimes unpredictable. What is Known: • Mitochondrial disorders are heterogenous and may present at any age, with any symptoms and any type of inheritance. • Mitochondrial disorders may be due to pathogenic variants in mitochondrial DNA (mtDNA) or nuclear genes (nDNA). What is New: • Since no single score system is satisfactorily accurate, a definite diagnosis is only possible with genetic studies with gene panels proving to be a cost-effective approach. • Clinical and biochemical features of patients without a confirmed diagnosis must be reviewed and other diagnosis must be considered. A wider genetic approach may be applied (WES or WGS).
原发性线粒体疾病在临床表现、生物化学和分子病因学方面具有高度的可变性。线粒体疾病可能是由线粒体、核基因组或两者之间相互作用中的遗传缺陷引起的。生化筛选测试可能不确定或具有误导性，因为患有明确的线粒体疾病的患者，特别是在儿科年龄，可能表现出正常的常规生化、肌肉组织学或线粒体呼吸链的酶分析。即使结合了多种标准（临床、生化、组织学和功能），诊断也常常具有挑战性，因为无数疾病会导致继发性线粒体功能障碍。如今，只有通过基因确认才能做出明确的诊断，因为没有单一的评分系统足够准确，其敏感性但特异性不高。结论：鉴于线粒体疾病的临床表现和生化特征具有异质性，临床怀疑可能不明显，因此医生之间的认识非常重要。在这篇综述中，我们提供了对疑似线粒体疾病患者的诊断方法以及慢性和急性治疗的信息。随访应提供患者状况的全面信息，因为这些疾病的干预大多是支持性的，预后是可变的，有时是不可预测的。已知的：• 线粒体疾病具有异质性，可能在任何年龄、任何症状和任何类型的遗传方式下出现。• 线粒体疾病可能是由于线粒体 DNA（mtDNA）或核基因（nDNA）中的致病性变异引起的。新的：• 由于没有单一的评分系统足够准确，只有通过基因研究，包括基因面板，才能做出明确的诊断，这被证明是一种具有成本效益的方法。• 必须重新审查没有明确诊断的患者的临床和生化特征，并考虑其他诊断。可以应用更广泛的基因方法（WES 或 WGS）。
