Clinical And Genetic Mutation Characteristics Of Methylmalonic Acidemia Associated Pulmonary Hypertension In 11 Children

Objective: To better understand methylmalonic acidemia(MMA)associated pulmonary hypertension(PH)by analyzing the characteristics of clinical presentation and gene mutation.Methods: 11 cases of pediatric patients with MMA associated PH from 2012 to 2018 were enrolled in this study.Their clinical data,laboratory tests,and auxiliary examinations were retrospectively reviewed.MMA gene mutation was analyzed.Standard treatment strategy was given and follow-up data were evaluated.Results1.Patient characteristics: 6 male and 5 female were diagnosed as MMA associated PH,with an average of(4.5±3.6)years.1 was early-onset type and 9 late-onset type.the age of onset of MMA associated PH was(4.3±3.3)years.the median time between onset and diagnosis was 2 months(range: 12 days to 1 year).2.Clinical features: The first symptoms of all 11 patients were associated PH,the main presentations included tachypnea,cyanosis,weakness,tachycardia and lower limb edema.world health organization functional classification(WHO FC)was Class II in 7,Class III in 3,Class IV in 1.Multi-system involvements were kidney in 7,anemia in 5,nervous system in 4,digestive system in 3,hypertension in 1.3.Laboratory tests: Median methylmalonic acid was 57.93,propinoylcarnitine(C3)was(10.03±5.39)umol/L,with C3/C2(0.48±0.20).Total blood Homocysteine(Hcy)level was severely elevated to(123.6±53.4)umol/L,median erythrocyte mean corpuscular volume(MCV)was 104.4fl,N terminal pro B type natriuretic peptide(NT-pro BNP)was elevated to(11594±10575)pg/ml.4.Pulmonary artery pressure: Pulmonary arterial systolic pressure(PASP)of 11 patients(76.0±13.8)mm Hg,mean pulmonary artery pressure(m PAP)of 3 patients was(59.7±16.4)mm Hg.5.Echocardiography: Atrial septal defect(ASD)in 2,ventricular septal defect(VSD)in 1,patent foramen ovale(PFO)in 1.6.Chest CT: A diffuse ground-glass nodular opacities in lungs in 6 of 9.7.Gene mutation: 6 mutations on MMACHC gene were found,with c.80A>G mutation in 8 cases and c.609G>A mutation in 6 cases.8.Treatment and follow-up: Standard treatment strategy to MMA was given to all 11 patients,PH targeted drugs was given to 8 patients.After treatment,Hcy and PASP dropped compared with each related value before treatment,respectively.2 patients died soon after discharge,and 1 patient lost to follow-up,symptoms resolved in all the other 8 patients,PASP became normal at the end of 6-12 moths′ follow-up.Conclusions1.MMA associated PH is more often seen in late-onset type of male patients,main presentations included tachypnea,cyanosis,other cardiovascular system involvements and Multi-system involvements may exist,diffuse lung disease(DLD)may be a cue.2.CblC type is main type of MMA associated PH,MMACHC gene c.80A>G and c.609G>A mutation may be the hot pints3.Standard treatment strategy to MMA and appropriate PH targeted drugs can make a good result.4.PH a novel way of presentation of MMA should be taken into account in the diagnosis of MMA,in view of the bad prognosis,enlarging the spectrum of inherited diseases that must be taken into account in the differential diagnosis of PH when there are presentations including tachypnea,cyanosis,elevated Hcy and MCV,especially a diffuse ground-glass nodular opacities in lungs.Objective :To explore the value of peripheral blood smear examination in screening and diagnosis of infantile-onset Pompe disease(IOPD)and to provide a basis for early diagnosis of this disease.Methods :The results of blood film examination were retrospectively analyzed from 29 patients with IOPD,which was diagnosed in our hospital during the period of 2013 to 2017 basing on enzymatic assay and genetic testing.Control values were obtained from 12 patients diagnosed with non-IOPD hypertrophic cardiomyopathy during the same period.Results :Vacuolated lymphocytes were detected in 36%(19~67%)of total lymphocytes in the IOPD group,compared with 0(0~6.7%)in the control group.In addition,periodic acid-schiff(PAS)stain-positive lymphocytes were detected in 36%(19~66%)of total lymphocytes in the IOPD group,compared with 0(0~6.0%)in the control group.There was a significant difference in the percentage of both vacuolated and PAS-positive lymphocytes between the two groups(P<0.01)and no overlap in distribution on the scatter plots.Conclusions :The blood film examination is cheap,rapid,minimally invasive,and provides a reliable screening tool to support a diagnosis of IOPD.