We report the case of an 11‐year‐old Syrian girl born to consanguineous parents, who presents an ataxic gait from early childhood. On clinical examination, she presented a severe static ‐ kinetic cerebellar syndrome, walking without support is possible for short distances only. Strikingly, three consecutive MRIs did not show any sign of cerebellar abnormalities, but a brain positron emission tomography (PET) using [18F]‐fluorodeoxyglucose (FDG) demonstrated a clear decrease in glucose metabolism in the cerebellum as well as the anterior and medial temporal lobe bilaterally. A clinical exome analysis identified a novel homozygous c.251A > G (p.Asn84Ser) likely pathogenic variant in the carbonic anhydrase 8 (CA8) gene. CA8 mutations cause cerebellar ataxia, mental retardation, and disequilibrium syndrome subtype 3 (CAMRQ3), a rare genetically autosomal recessive disorder, only described in four families, so far with the frequent observation of quadrupedal gait. The proband differed with other reported CA8 mutations by the absence of clear cerebellar signs on brain MRI and the presence of focal seizures. This report expands the clinical spectrum associated with mutations in CA8 and illustrates the possible discrepancy between (mild) neuro‐radiological images (MRI) and (severe) clinical phenotype in young individuals. In contrast, the observation of clear cerebellar abnormal metabolic findings suggests that the FDG‐PET scan may be used as an early marker for hereditary ataxia.

中文翻译：

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碳酸酐酶 8 基因的新型纯合变体扩展了小脑共济失调、智力低下和失衡综合征亚型 3 的表型。

我们报告了一名 11 岁叙利亚女孩的病例，她是近亲父母所生，她从小就表现出共济失调的步态。在临床检查中，她出现了严重的静态-动力小脑综合征，只能在短距离的情况下在没有支撑的情况下行走。引人注目的是，连续 3 次 MRI 未显示任何小脑异常迹象，但使用 [18F]-氟脱氧葡萄糖 (FDG) 进行的脑正电子发射断层扫描 (PET) 显示小脑以及前颞叶和内侧颞叶的葡萄糖代谢明显下降双侧叶。临床外显子组分析确定了碳酸酐酶 8 (CA8) 基因中的一种新的纯合 c.251A > G (p.Asn84Ser) 可能致病变异。CA8 突变导致小脑共济失调、智力迟钝和失衡综合征亚型 3 (CAMRQ3)，一种罕见的遗传性常染色体隐性遗传病，仅在四个家族中描述，迄今为止经常观察到四足步态。先证者与其他报道的 CA8 突变的不同之处在于脑 MRI 上没有明显的小脑体征和局灶性癫痫发作。本报告扩展了与 CA8 突变相关的临床谱，并说明了年轻个体（轻度）神经放射图像（MRI）和（严重）临床表型之间可能存在的差异。相比之下，观察到明显的小脑异常代谢发现表明 FDG-PET 扫描可用作遗传性共济失调的早期标志物。先证者与其他报道的 CA8 突变的不同之处在于脑 MRI 上没有明显的小脑体征和局灶性癫痫发作。本报告扩展了与 CA8 突变相关的临床谱，并说明了年轻个体（轻度）神经放射图像（MRI）和（严重）临床表型之间可能存在的差异。相比之下，观察到明显的小脑异常代谢发现表明 FDG-PET 扫描可用作遗传性共济失调的早期标志物。先证者与其他报道的 CA8 突变的不同之处在于脑 MRI 上没有明显的小脑体征和局灶性癫痫发作。本报告扩展了与 CA8 突变相关的临床谱，并说明了年轻个体（轻度）神经放射图像（MRI）和（严重）临床表型之间可能存在的差异。相比之下，观察到明显的小脑异常代谢发现表明 FDG-PET 扫描可用作遗传性共济失调的早期标志物。