Russo Sam Nicholas, Goldstein Amy, Karaa Amel, Koenig Mary Kay, Walker Melissa
Division of Child and Adolescent Neurology, Department of Pediatrics, The University of Texas McGovern Medical School, Houston, TX, USA.
Mitochondrial Medicine Frontier Program, Division of Human Genetics, Children's Hospital of Philadelphia, PA, USA.
Child Neurol Open. 2021 Mar 2;8:2329048X21991382. doi: 10.1177/2329048X21991382. eCollection 2021 Jan-Dec.
In the field of mitochondrial medicine, correlation of clinical phenotype with mutation heteroplasmy remains an outstanding question with few, if any, clear thresholds corresponding to a given phenotype. The m.8344A>G mutation is most commonly associated with myoclonus epilepsy and ragged red fiber syndrome (MERRF) at varying levels of heteroplasmy. However, a handful of cases been previously reported in which individuals homoplasmic or nearly homoplasmic for this mutation in the blood have presented with multiple bulbar palsies, respiratory failure, and progressive neurologic decline almost uniformly following a respiratory illness. MRI brain in all affected individuals revealed symmetric T2 hyperintense lesions of subcortical gray matter structures, consistent with Leigh syndrome. Here, we present 3 cases with clinical, biochemical, and neuro-imaging findings with the additional reporting of spinal lesions. This new phenotype supports a heteroplasmy-dependent phenotype model for this mutation and recognition of this can help clinicians with diagnosis and anticipatory clinical guidance.
在线粒体医学领域，临床表型与突变异质性之间的相关性仍然是一个突出问题，几乎没有明确对应特定表型的阈值。m.8344A>G突变在不同程度的异质性下，最常与肌阵挛性癫痫伴破碎红纤维综合征（MERRF）相关。然而，先前已有少数病例报道，血液中该突变呈纯合或近乎纯合状态的个体，几乎均在呼吸道疾病后出现多发性延髓麻痹、呼吸衰竭和进行性神经功能衰退。所有受影响个体的脑部MRI显示皮质下灰质结构对称的T2高信号病变，符合 Leigh 综合征。在此，我们报告3例具有临床、生化和神经影像学表现的病例，并额外报告了脊髓病变。这种新表型支持该突变的异质性依赖表型模型，认识到这一点有助于临床医生进行诊断和提供前瞻性临床指导。
