摘要
目的:总结15例以肺高血压(pulmonary hypertension,PH)为突出表现的甲基丙二酸尿症(methylmalonic aciduria,MMA)患儿临床特点及基因检测结果,提高对甲基丙二酸尿症相关PH临床表现的认识及诊治水平。方法:回顾性分析2012年5月至2016年5月北京大学第一医院儿科诊断治疗的15例以PH为突出表现的MMA患儿临床特点、诊断治疗经过、基因突变分析及随访结果,MMA的诊断标准为尿中甲基丙二酸水平>正常值的100倍,检测血浆总同型半胱氨酸(homocysteine,Hcy)和脑利钠肽(brain natriuretic peptide,BNP)水平。PH的诊断标准采用多普勒超声经三尖瓣反流估测的肺动脉收缩压(pulmonary arterial systolic pressure,PASP)>40 mm Hg(1 mm Hg=0.133 k Pa)。结果:(1)起病特点:15例患儿中男10例,女5例,年龄0.5~13.8岁,平均(5.0±4.3)岁,PH起病年龄(3.7±3.5)岁,其中早发型5例,晚发型10例,10例PH症状为MMA首发表现,5例在MMA起病后3~72个月出现PH症状。(2)临床表现:气促和/或呼吸困难11例,口唇发绀11例,乏力和/或活动耐力下降6例,水肿4例;PH国际卫生组织功能分级(WHO FC)为Ⅱ级4例,Ⅲ级5例,Ⅵ级6例,平均(3.1±0.8)级。(3)多系统损害:肾损害14例,表现为血尿及蛋白尿,5例为慢性肾脏病(chronic kidney disease,CKD),8例大细胞性贫血,4例伴轻-中度智力运动发育落后,5例亚临床甲状腺功能减低。(4)辅助检查:15例患儿经超声心动图三尖瓣反流测量的肺动脉收缩压49~135 mm Hg,平均(90.3±23.9)mm Hg;血浆总Hcy显著升高[35.0~221.0μmol/L,平均(121.2±48.2)μmol/L],其中11例>100μmol/L;12例血BNP水平不同程度升高[21.0~4995.0 ng/L,中位值794 ng/L,其中12例>300 ng/L],血气分析发现存在不同程度低氧血症,动脉血氧饱和度平均81.4%±8.4%(70%~94%)。(5)肺部高分辨CT(high resolusion CT,HRCT):9例小叶中心磨玻璃密度结节及肺小叶间隔增厚,提示肺静脉闭塞病(pulmonary veno-occlusive disease,POVD),其中3例伴肺部炎症或肺�
Objective: To deepen our understanding of Methylmalonic aciduria( MMA) associated pulmonary hypertension( PH) by analyzing the characteristics of clinical presentation,pulmonary high resolusion CT( HRCT),treatment response and gene mutation. Methods: This study includes 15 cases of pediatric patients with MMA associated PH diagnosed and treated in Peking University First Hospital pediatric department between May 2012 and May 2016 with symptoms of PH as their leading presentation. Clinical symptoms and signs were recorded,Routine blood laboratory examinations was done including arterial blood gas analysis. Plasma total homocysteine( Hcy) and brain natriuretic peptide( BNP) level were measured. MMA gene mutation was analyzed. Chest HRCT was done in most of the patients. Standard treatment strategy to MMA and PH was given and follow up study was done,and the related literature was reviewed. Statistical analysis was done. The diagnosis of MMA was made by methylmalonic acid level > 100 times the normal value in the urine. The diagnosis of PH was made by pulmonary arterial systolic pressure( PASP) > 40 mm Hg,which was estimated by the measurement of tricuspid regurgitation velocity through Doppler Echocardiography. Results:( 1) Patient characteristics: There were 10 male and 5 female patients diagnosed as MMA associated PH,aged 0. 5 to 13. 8 years,with an average of( 5. 0 ± 4. 3) years. The age of onset of PH was( 3. 7 ± 3. 5) years,with an early onset type MMA in 5cases and late-onset type in 10 cases.( 2) Clinical presentation: Among the 15 cases of MMA,the first symptoms were associated with PH in 10 cases,so PH and MMA were diagnosed at the same time,and PH was diagnosed 3 to 72 months post MMA presentation in the other 5 cases. The main presentations of PH were techypnea/dyspnea and cyanosis in 11 cases each,weakness and fatigue on exertion in 6 cases,and edema in 4 cases. PH WHO functional classification( WHO FC) was ClassⅡin 4,Class Ⅲ in 5and Class Ⅵ in 6 cases,with an average of Class 3. 1 ± 0. 8. Mult
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2017年第5期768-777,共10页
Journal of Peking University:Health Sciences
