Department of Pediatrics, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
Department of Pediatrics, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
BMC Pediatr. 2021 Oct 16;21(1):453. doi: 10.1186/s12887-021-02923-6.
Severe protein C deficiency is a rare and inherited cause of thrombophilia in neonates. Protein C acts as an anticoagulant, and its deficiency results in vascular thrombosis. Herein, we report a case of protein C deficiency with a homozygous pathogenic variant in a term neonate, with good outcomes after proper treatment.
A four-day-old male newborn was transferred to the Seoul National University Hospital on account of dark red to black skin lesions. He was born full-term with an average birth weight without perinatal problems. There were no abnormal findings in the prenatal tests, including intrauterine sonography. The first skin lesion was observed on his right toes and rapidly progressed to proximal areas, such as the lower legs, left arm, and buttock. Under the impression of thromboembolism or vasculitis, we performed a coagulopathy workup, which revealed a high D-dimer level of 23.05 μg/ml. A skin biopsy showed fibrin clots in most capillaries, and his protein C activity level was below 10%, from which we diagnosed protein C deficiency. On postnatal day 6, he experienced an apnea event with desaturation and an abnormal right pupillary light reflex. Brain computed tomography showed multifocal patchy intracranial hemorrhage and intraventricular hemorrhage with an old ischemic lesion. Ophthalmic examination revealed bilateral retinal traction detachments with retinal folds. Protein C concentrate replacement therapy was added to previous treatments including steroids, prostaglandin E1, and anticoagulation. After replacement therapy, there were no new skin lesions, and the previous lesions recovered with scarring. Although there were no new brain hemorrhagic infarctions, there was ongoing ischemic tissue loss, which required further rehabilitation. Ophthalmic surgical interventions were performed to treat the bilateral retinal traction detachments with retinal folds. Molecular analysis revealed a homozygous pathogenic variant in the PROC gene.
Severe protein C deficiency can manifest as a fatal coagulopathy in any organ. Early diagnosis and proper treatment, including protein C concentrate replacement, may improve outcomes without serious sequelae.
严重蛋白 C 缺乏症是新生儿血栓形成的一种罕见且遗传性病因。蛋白 C 作为一种抗凝剂，其缺乏会导致血管血栓形成。在此，我们报告了一例足月新生儿蛋白 C 缺乏症，存在纯合致病性变异，经适当治疗后结局良好。
一名 4 天大的男性新生儿因皮肤出现暗红色至黑色斑疹而转入首尔国立大学医院。他足月出生，体重正常，无围产期问题。产前检查无异常发现，包括宫内超声检查。他的右侧脚趾出现第一个皮损，并迅速向小腿、左臂和臀部等近端部位进展。鉴于血栓栓塞或血管炎的印象，我们进行了凝血功能障碍检查，结果显示 D-二聚体水平较高（23.05μg/ml）。皮肤活检显示大多数毛细血管中有纤维蛋白凝块，其蛋白 C 活性水平低于 10%，由此我们诊断为蛋白 C 缺乏症。在出生后第 6 天，他出现呼吸暂停伴血氧饱和度下降和右侧瞳孔光反射异常。脑计算机断层扫描显示多灶性斑片状颅内出血和伴有陈旧性缺血性病变的脑室内出血。眼科检查显示双侧视网膜牵拉性脱离伴视网膜褶皱。在之前的治疗方案中（包括类固醇、前列腺素 E1 和抗凝治疗）加入了蛋白 C 浓缩物替代治疗。替代治疗后，未出现新的皮肤损伤，先前的皮肤损伤已恢复并留有瘢痕。尽管没有新的脑出血性梗死，但仍有持续的缺血性组织损失，需要进一步康复。眼科手术干预用于治疗双侧视网膜牵拉性脱离伴视网膜褶皱。分子分析显示 PROC 基因存在纯合致病性变异。
严重蛋白 C 缺乏症可在任何器官表现为致命性凝血功能障碍。早期诊断和适当治疗，包括蛋白 C 浓缩物替代治疗，可能改善结局，避免严重后遗症。
