Inborn errors of metabolism can cause epileptic encephalopathies. Biallelic loss-of-function variants in the ITPA gene, encoding inosine triphosphate pyrophosphatase (ITPase), have been reported in epileptic encephalopathies with lack of myelination of the posterior limb of the internal capsule, brainstem tracts, and tracts to the primary visual and motor cortices (MIM:616647). ITPase plays an important role in purine metabolism. In this study, we identified two novel homozygous ITPA variants, c.264-1 G > A and c.489-1 G > A, in two unrelated consanguineous families. The probands had epilepsy, microcephaly with characteristic magnetic resonance imaging findings (T2 hyperintensity signals in the pyramidal tracts of the internal capsule, delayed myelination, and thin corpus callosum), hypotonia, and developmental delay; both died in early infancy. Our report expands the knowledge of clinical consequences of biallelic ITPA variants.

中文翻译：

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新型ITPA变异体会导致癫痫性脑病，并伴有多器官功能障碍。

天生的新陈代谢错误可引起癫痫性脑病。据报道，在癫痫性脑病中，ITPA基因的双等位基因功能丧失型变体编码肌苷三磷酸焦磷酸酶（ITPase），缺乏内囊后肢，脑干道和初级视力和运动道的髓鞘化。皮质（MIM：616647）。ITPase在嘌呤代谢中起重要作用。在这项研究中，我们在两个不相关的近亲家庭中鉴定了两个新颖的纯合ITPA变体c.264-1 G> A和c.489-1 G>A。先证者患有癫痫，小头畸形，并具有特征性的磁共振成像表现（内囊锥体束中的T2高信号，延迟的髓鞘形成和thin体变薄），肌张力低下和发育迟缓。都死于婴儿早期。我们的报告扩展了双等位基因ITPA变体的临床后果知识。