Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Genetics Division, Sandor Specialty Diagnostic Pvt Ltd, Hyderabad, Telangana, India.
Neuropediatrics. 2022 Jun;53(3):167-175. doi: 10.1055/s-0042-1742322. Epub 2022 Jan 28.
Inosine triphosphate pyrophosphohydrolase (ITPase) deficiency associated with mutations in the 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 -associated neurodegeneration and two pathogenic compound heterozygous variants. We also reviewed the previously published cases of -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 ( = 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%).
-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.
与 基因突变相关的肌苷三磷酸焦磷酸水解酶（ITPase）缺乏症是一种新近被描述的嘌呤代谢途径缺陷，表现为早发性婴儿癫痫性脑病和致死性病程。这种疾病较为罕见，全世界仅报道了 12 例。
我们报告了另外两例与 相关的神经退行性疾病和两个致病性复合杂合变体。我们还回顾了先前报道的与 相关的脑病病例。
两例患者均表现为进行性婴儿期起病的脑病、严重的发育迟缓、小头畸形、面部畸形和癫痫。加上已报道的两例病例，共有 14 例病例可用于分析。起病的平均年龄为 16.7±12.4 个月（范围 3-48 个月）。起病时最常见的临床特征是发育迟缓、癫痫、小头畸形和肌张力低下，14 例（100%）患者均有此表现。癫痫发作的平均年龄为 4.75 个月（范围 2-14 个月）。在明确评估的 42%（5/12）患者中发现了心肌病。77%（9/12）的病例报告了近亲结婚。主要的神经影像学特征是 T2 信号异常和长束弥散受限，特别是内囊后肢和视辐射。大多数患者在 4 岁之前死亡（85.7%）。
与 相关的脑病表现为婴儿期起病的神经退行性变、进行性小头畸形和癫痫。进行性脑萎缩和白质束弥散受限是重要的影像学线索。
