Srivastava Siddharth, Gubbels Cynthia S, Dies Kira, Fulton Anne, Yu Timothy, Sahin Mustafa
1 Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
2 Division of Genetics & Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
J Child Neurol. 2017 Aug;32(9):840-845. doi: 10.1177/0883073817711527. Epub 2017 May 25.
ACO2 encodes aconitase 2, catalyzing the second step of the tricarboxylic acid. To date, there are only 6 reported families with 5 unique ACO2 mutations. Affected individuals can develop intellectual disability, epilepsy, brain atrophy, hypotonia, ataxia, optic atrophy, and retinal degeneration. Here, we report an 18-year-old boy with a novel ACO2 variant discovered on whole-exome sequencing. He presented with childhood-onset ataxia, impaired self-help skills comparable to severe-profound intellectual disability, intractable epilepsy, cerebellar atrophy, peripheral neuropathy, optic atrophy, and pigmentary retinopathy. His variant is the sixth unique ACO2 mutation. In addition, compared to mild cases (isolated optic atrophy) and severe cases (infantile death), our patient may be moderately affected, evident by increased survival and some preserved cognition (ability to speak full sentences and follow commands), which is a novel presentation. This case expands the disease spectrum to include increased survival with partly spared cognition.
ACO2编码乌头酸酶2，催化三羧酸循环的第二步。迄今为止，仅报道了6个家族，有5种独特的ACO2突变。受影响的个体可出现智力残疾、癫痫、脑萎缩、肌张力减退、共济失调、视神经萎缩和视网膜变性。在此，我们报告一名18岁男孩，通过全外显子测序发现了一种新的ACO2变异。他表现为儿童期起病的共济失调、自理能力受损，相当于重度至极重度智力残疾、难治性癫痫、小脑萎缩、周围神经病变、视神经萎缩和色素性视网膜病变。他的变异是第六种独特的ACO2突变。此外，与轻症病例（孤立性视神经萎缩）和重症病例（婴儿死亡）相比，我们的患者可能受到中度影响，这表现为生存期延长和部分认知能力保留（能说完整句子并听从指令），这是一种新的表现形式。该病例扩大了疾病谱，包括生存期延长且部分认知功能保留。
