Da-Silva Shonola S, Sajan Imran S, Underwood Joseph P
Division of Pediatric Critical Care Medicine, Children's Regional Hospital, University Medical Center, Camden, New Jersey 08103, USA.
Pediatrics. 2003 Aug;112(2):e158-61. doi: 10.1542/peds.112.2.e158.
Cyanosis is a physical finding that can occur at any age but presents the greatest challenge when it occurs in the newborn. The cause is multiple, and it usually represents an ominous sign, especially when it occurs in association with neonatal sepsis, cyanotic congenital heart disease, and airway abnormalities. Cyanosis caused by abnormal forms of hemoglobin can also be life-threatening, and early recognition is mandatory to prevent unnecessary investigations and delay in management. Abnormal hemoglobin, such as hemoglobin M, is traditionally discovered by electrophoresis, so the newborn screen, which is mandatory in several states, is a useful tool for the diagnosis. Although acquired methemoglobinemia, caused by environmental oxidizing agents, is common, congenital deficiency of the innate reducing enzyme is so rare that only a few cases are documented in the medical literature around the world. We present a neonate with cyanosis as a result of congenital deficiency of the reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase enzyme. This infant was found to be blue at a routine newborn follow-up visit. Sepsis, structural congenital heart disease, prenatal administration, and ingestion of oxidant dyes were excluded as a cause of the cyanosis by history and appropriate tests. Chocolate discoloration of arterial blood provided a clue to the diagnosis. A normal newborn screen and hemoglobin electrophoresis made the diagnosis of hemoglobin M unlikely as the cause of the methemoglobinemia (Hb A 59.4%, A2 1.8%, and F 38.8%). Red blood cell enzyme activity and DNA analysis revealed a homozygous form of the cytochrome b5 reductase enzyme deficiency. He responded very well to daily methylene blue and ascorbic acid administration, and he has normal growth and developmental parameters, although he shows an exaggerated increase in his methemoglobin level with minor oxidant stress such as diarrhea.
发绀是一种可在任何年龄出现的体征，但在新生儿中出现时面临的挑战最大。其病因多种多样，通常是不祥之兆，尤其是与新生儿败血症、青紫型先天性心脏病及气道异常同时出现时。由异常形式血红蛋白引起的发绀也可能危及生命，早期识别对于避免不必要的检查及治疗延误至关重要。传统上，异常血红蛋白如血红蛋白M是通过电泳发现的，因此在多个州强制进行的新生儿筛查是诊断的有用工具。虽然由环境氧化剂导致的后天性高铁血红蛋白血症很常见，但先天性还原酶缺乏极为罕见，全球医学文献中仅有少数病例记载。我们报告一例因先天性烟酰胺腺嘌呤二核苷酸-细胞色素b5还原酶缺乏导致发绀的新生儿。该婴儿在常规新生儿随访时被发现皮肤发蓝。通过病史及适当检查排除了败血症、先天性结构心脏病、产前用药及摄入氧化性染料作为发绀病因。动脉血巧克力样变色为诊断提供了线索。正常的新生儿筛查及血红蛋白电泳排除了血红蛋白M作为高铁血红蛋白血症病因的可能（血红蛋白A 59.4%，A2 1.8%，F 38.8%）。红细胞酶活性及DNA分析显示为细胞色素b5还原酶缺乏的纯合形式。他对每日给予亚甲蓝和维生素C反应良好，生长发育参数正常，不过在轻微氧化应激如腹泻时，其高铁血红蛋白水平会过度升高。
