title: Biochemical, molecular and outcome analysis of eight chinese asymptomatic individuals with methyl malonic acidemia detected through newborn screening.
abstract: Methyl malonic academia (MMA) is characterized by abnormal accumulation of methyl malonic acid in body fluids. Patients usually have a variety of clinical symptoms including recurrent vomiting, metabolic acidosis, developmental delay, seizure, or death. However, a few cases where the patients have no symptom are also reported. Here, we conducted clinical, biochemical, and molecular analysis of eight Chinese patients identified through newborn screening between 2003 and 2013. All the patients had significantly higher blood propionylcarnitine (C3) concentrations, ratio of propionylcarnitine/acetylcarnitine (C3/C2); and their urine methyl malonic acid and methylcitric acid (MCA) excretions were remarkably higher than normal at diagnosis and during follow-ups. In addition, five different known mutations were identified in seven of the eight patients in either MUT or MMACHC. All these mutations were expected to produce defective proteins that would result in decreased or even total loss of methyl malonyl-CoA mutase activity. However, normal outcomes were found in all patients in physical growth, intellectual performance and cerebral MRI analysis at diagnosis (range, 14-53 days) and during follow-ups (range, 1.8-10 years). Our study is the first report of Chinese MMA patients with increased secretion of methyl malonic acid and molecular defects in MUT or MMACHC yet remain asymptomatic.
authors.affiliation: Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Lianshu
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Department of Pediatric Endocrinology and Genetic Metabolism, Zhengzhou Children's Hospital, Henan, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Zhuwen
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Xuefan
authors.initials: X
authors.lastname: Gu
mesh_terms: D000108:Acetylcarnitine / Q000097:blood; D000138:Acidosis / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D044466:Asian People; D058070:Asymptomatic Diseases; D002262:Carboxy-Lyases / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002951:Citrates / Q000652:urine; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008314:Malonates / Q000097:blood* / Q000652:urine; D008316:Malonyl Coenzyme A / Q000097:blood / Q000235:genetics; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D008764:Methylmalonic Acid / Q000097:blood; D008765:Methylmalonyl-CoA Mutase / Q000235:genetics*; D009154:Mutation; D015997:Neonatal Screening; D010088:Oxidoreductases
chemical_list: D002352:Carrier Proteins; D002951:Citrates; D008314:Malonates; C003223:propionylcarnitine; D008316:Malonyl Coenzyme A; C031605:2-methylcitric acid; D000108:Acetylcarnitine; D008764:Methylmalonic Acid; C508359:MMACHC protein, human; D010088:Oxidoreductases; D002262:Carboxy-Lyases; D008765:Methylmalonyl-CoA Mutase; C005230:methyl malonate; D002331:Carnitine
keywords: asymptomatic; methyl malonic academia; methyl malonic acid; new born screening