Objective: To improve the awareness of methylmalonic acidemia and hyperhomocysteinemia with diffuse lung disease as an initial or main presentation. Methods: A retrospective analysis of the clinical manifestations, radiological features, laboratory tests, genetic variations, treatments and prognoses was conducted in six children presented with diffuse lung disease and finally diagnosed with methylmalonic acidemia and hyperhomocysteinemia in Ward 2 of Department of Respiratory Diseases, Beijing Children's Hospital, from August 2017 to November 2018. Results: Six children were included in this study. Two children were male and four were female. The average age of onset was 28 months. The mean age at diagnosis was 34 months. The average interval from onset to diagnosis was 6 months. Four children who underwent genetic tests were found to have variants of gene MMACHC and diagnosed with CblC type. All children had respiratory symptoms and signs as initial or main presentation, which were tachypnea (5 cases), exercise intolerance (5 cases), cough (4 cases), cyanosis (4 cases), clubbing (4 cases), dyspnea (3 cases) and retractions (3 cases). Pulmonary arterial hypertension was found in all six children. Pericardial effusion (4 cases), kidney involvement (3 cases), nervous system involvement (3 cases), gastrointestinal system involvement (3 cases) and anemia (2 cases) also coexisted. The high resolution computed tomography (HRCT) features included dilated pulmonary artery (6 cases), ground-glass opacities (4 cases), diffuse poorly defined ground-glass centrilobular nodules (3 cases), pleural effusion (3 cases), thickening of interlobular septum (2 cases), etc. All children had an elevated concentration of methylmalonic acid in urine and homocysteine in plasma. Genetic tests were performed in four patients, and MMACHC genetic mutations were found in all of them. Clinical manifestations, HRCT features and pulmonary arterial hypertension turned better in five children after treatment. One patient who was not regularly followed-up died. Conclusions: Pulmonary involvement including diffuse lung disease and pulmonary arterial hypertension could coexist with methylmalonic acidemia and hyperhomocysteinemia, which may have respiratory symptoms and signs as the initial or main presentation. Characteristic HRCT features were found in some patients. Plasma homocysteine test is a quick method for screening the disease in children with diffuse lung disease and (or) pulmonary arterial hypertension. Both diffuse lung disease and pulmonary arterial hypertension may turn better after treatment.
目的： 探讨因弥漫性肺疾病就诊确诊为甲基丙二酸血症合并高同型半胱氨酸血症患儿的临床特点。 方法： 对2017年8月至2018年11月在首都医科大学附属北京儿童医院呼吸二科确诊的以弥漫性肺疾病为突出或首发表现的6例甲基丙二酸血症合并高同型半胱氨酸血症患儿（男2例、女4例）的临床表现、影像学特点、实验室检查、基因变异类型、治疗及预后进行回顾性分析。 结果： 6例患儿平均发病年龄为2岁4月龄，平均确诊年龄为2岁10月龄，平均诊断周期为6个月，4例患儿经基因检测明确MMACHC变异，提示为钴胺素C型。6例患儿均以呼吸系统表现为主要或首发表现就诊，常见症状及体征为气促5例、活动耐力下降5例，咳嗽4例、发绀4例、杵状指4例、呼吸困难3例、三凹征3例。除呼吸系统外，6例均伴肺动脉高压。此外，伴心包积液4例，伴肾脏受累3例，伴神经系统受累3例，伴消化系统受累3例，伴贫血2例。高分辨率肺CT表现为肺动脉增宽6例、磨玻璃影4例、多发边缘模糊的小叶中心磨玻璃样结节影3例、胸腔积液3例、网格影2例等。所有患儿均伴尿甲基丙二酸及血同型半胱氨酸增高。4例患儿行基因检测，均为MMACHC基因变异。经治疗后5例患儿呼吸道症状、肺部影像学及肺动脉高压均好转，血同型半胱氨酸明显下降，1例未规律随访患儿死亡。 结论： 甲基丙二酸血症合并高同型半胱氨酸血症可以肺部病变为主要表现，出现弥漫性肺疾病及肺动脉高压。可以呼吸系统表现起病，伴有多系统受累，部分患儿具有特征性的肺部影像学表现。血同型半胱氨酸检测可作为弥漫性肺疾病和（或）肺动脉高压儿童的快速筛查手段。经治疗弥漫性肺疾病及肺动脉高压均可能好转。.
Keywords: Child; Hyperhomocysteinemia; Hypertension, pulmonary; Lung diseases, interstitial; Methylmalonic acid.