Metabolic Disease Unit, Meyer Children's Hospital, Florence, Italy.
IRCCS Stella Maris Foundation, Molecular Medicine for Neurodegenerative and Neuromuscular Disease Unit, Pisa, Italy.
Clin Genet. 2022 Feb;101(2):260-264. doi: 10.1111/cge.14088. Epub 2021 Nov 22.
Bi-allelic alterations in the MDH2 gene have recently been reported in three unrelated toddlers with early-onset severe encephalopathy. Here, we describe a new case of a child carrying novel variants in MDH2. This child presented with early-onset encephalocardiopathy requiring heart transplant and showed cerebellar ataxia and drug-responsive epilepsy; his family history was significant for multiple cancers, a feature often associated with monoallelic variants in MDH2. Functional studies in cultured skin fibroblasts from the proband showed reduced protein levels and impaired enzyme activity, further corroborating the genetic results. The relatively mild neurological presentation and severe cardiac manifestations requiring heart transplant distinguish this case from previous reports. This patient thus expands the spectrum of clinical features associated with MDH2 variants.
最近有报道称，3 名无关联的幼儿患有早发性严重脑病，其 MDH2 基因存在双等位基因改变。在这里，我们描述了一个携带 MDH2 新变异的患儿的新病例。该患儿表现为早发性心脏脑病，需要心脏移植，并出现小脑共济失调和药物反应性癫痫；其家族史存在多种癌症，这一特征通常与 MDH2 的单等位基因变异有关。来自先证者的培养皮肤成纤维细胞的功能研究显示蛋白水平降低和酶活性受损，进一步证实了遗传结果。相对较轻的神经表现和严重的心脏表现需要心脏移植，这使该病例与以往报告有所不同。因此，该患者扩展了与 MDH2 变异相关的临床特征谱。
