与ITPA基因突变相关的肌苷三磷酸焦磷酸水解酶(ITPase)缺乏症是最近表征的嘌呤途径缺陷,表现为早期婴儿癫痫性脑病和致死过程。这种疾病很罕见,全世界仅报告了12例病例。
我们报告了另外两例与ITPA相关的神经变性和两种致病复合杂合变异。我们还回顾了以前发表的ITPA相关脑病病例。
两例均表现为进行性婴幼儿型脑病,严重的发育迟缓,小头畸形,面部畸形,和癫痫。加上提出的两个案例,14例病例可供分析。出现的平均年龄为16.7±12.4个月(范围3-48m)。出现时最常见的临床特征是发育迟缓,癫痫发作,小头畸形,和低张力,在所有14(100%)患者中观察到。癫痫发作的平均年龄为4.75个月(范围2-14m)。42%的患者明确评估了心肌病(n=5/12)。77%的病例报告有血缘关系。主要的神经放射学特征是T2信号异常和长束中的弥散限制,尤其是内囊的后肢和视神经辐射。大多数患者在4岁之前死亡(85.7%)。
ITPA相关性脑病表现为婴儿发作的神经变性,进行性小头畸形,和癫痫。进行性脑萎缩和白质束的弥散限制是重要的放射学线索。
Inosine triphosphate pyrophosphohydrolase (ITPase) deficiency associated with mutations in the ITPA gene is a recently characterized purine pathway defect that presents with early infantile epileptic encephalopathy and lethal course. This disorder is rare, and only 12 cases are reported worldwide.
We report two additional cases of ITPA-associated neurodegeneration and two pathogenic compound heterozygous variants. We also reviewed the previously published cases of ITPA-associated encephalopathy.
Both cases presented with progressive infantile-onset encephalopathy, severe developmental delay, microcephaly, facial dysmorphism, and epilepsy. Together with the presented two cases, 14 cases were available for analysis. The mean age of presentation was 16.7 ± 12.4 months (range 3-48 m). The most common clinical features at presentation were developmental delay, seizures, microcephaly, and hypotonia, seen in all 14 (100%) patients. The mean age of seizure onset was 4.75 months (range 2-14 m). Cardiomyopathy was noted in 42% of patients where it was explicitly evaluated (n = 5/12). Consanguinity was reported in 77% of the cases. The cardinal neuroradiological features are T2-signal abnormalities and diffusion restriction in the long tracts, especially the posterior limb of the internal capsule and the optic radiation. The majority of the patients died before 4 years of age (85.7%).
ITPA-related encephalopathy presents with infantile-onset neurodegeneration, progressive microcephaly, and epilepsy. Progressive brain atrophy and diffusion restriction in the white matter tracts are important radiological clues.