Background 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.

Methods 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.

Results 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%).

Conclusion 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.

背景与ITPA基因 突变相关的三磷酸肌苷焦磷酸水解酶 (ITPase) 缺乏是最近发现的一种嘌呤途径缺陷，表现为早期婴儿癫痫性脑病和致死病程。这种疾病很少见，全世界仅报告 12 例。

方法 我们报告了另外两例ITPA相关神经变性和两种致病性复合杂合变异体。我们还回顾了以前发表的ITPA相关脑病病例。

结果 两例病例均出现进行性婴儿型脑病、严重发育迟缓、小头畸形、面部畸形和癫痫。连同提出的两个案例，有 14 个案例可供分析。就诊的平均年龄为 16.7 ± 12.4 个月（范围 3-48 m）。就诊时最常见的临床特征是发育迟缓、癫痫发作、小头畸形和肌张力减退，在所有 14 名 (100%) 患者中均可见。癫痫发作的平均年龄为 4.75 个月（范围 2-14 m）。在明确评估的患者中，有 42% 的患者出现了心肌病（n = 5/12)。77%的病例报告了血缘关系。主要的神经放射学特征是 T2 信号异常和长束弥散受限，尤其是内囊后肢和视辐射。大多数患者在 4 岁前死亡（85.7%）。

结论 ITPA相关脑病表现为婴儿期神经变性、进行性小头畸形和癫痫。白质束中进行性脑萎缩和弥散受限是重要的放射学线索。