We report a patient with profound congenital hypotonia, central hypoventilation, poor visual behaviour with retinal hypopigmentation, and significantly decreased mitochondrial respiratory chain complex I activity in muscle, who died at 7 months of age having made minimal developmental progress. Biallelic predicted truncating P4HTM variants were identified following trio whole-genome sequencing, consistent with a diagnosis of hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy and eye abnormalities (HIDEA) syndrome. Very few patients with HIDEA syndrome have been reported previously and mitochondrial abnormalities were observed in three of four previous cases who had a muscle biopsy, suggesting the possibility that HIDEA syndrome represents a primary mitochondrial disorder. P4HTM encodes a transmembrane prolyl 4-hydroxylase with putative targets including hypoxia inducible factors, RNA polymerase II and activating transcription factor 4, which has been implicated in the integrated stress response observed in cell and animal models of mitochondrial disease, and may explain the mitochondrial dysfunction observed in HIDEA syndrome.

我们报告了一名患有严重的先天性肌张力减退、中枢性通气不足、视觉行为不佳和视网膜色素减退以及肌肉中线粒体呼吸链复合物 I 活性显着降低的患者，该患者在 7 个月大时死亡，发育进展很小。在三重全基因组测序后鉴定出双等位基因预测的截断P4HTM变体，与肌张力减退、通气不足、智力障碍、自主神经功能障碍、癫痫和眼部异常 (HIDEA) 综合征的诊断一致。之前报道的 HIDEA 综合征患者很少，并且在之前进行过肌肉活检的 4 例病例中有 3 例观察到线粒体异常，这表明 HIDEA 综合征可能代表原发性线粒体疾病。P4HTM编码一种跨膜脯氨酰 4-羟化酶，其推定的靶点包括缺氧诱导因子、RNA 聚合酶 II 和激活转录因子 4，这与在线粒体疾病的细胞和动物模型中观察到的综合应激反应有关，并可能解释线粒体功能障碍在 HIDEA 综合征中观察到。