title: [Abnormal findings during newborn period of 160 patients with early-onset methylmalonic aciduria].
abstract: OBJECTIVE
  Methylmalonic aciduria is the most common disorder of organic acidurias in the mainland of China. It is also the one of treatable metabolic disorders. The clinical spectrum of the patients varies from severe neonatal-onset forms with neonatal brain injury and high mortality to milder forms with adult-onset. The clinical manifestations of neonates with methylmalonic aciduria are non-specific. Early diagnosis and adequate treatment contribute a lot to improving the prognosis of the patients. In this study, the abnormal clinical and laboratory findings in neonatal period of 160 Chinese patients with early-onset methylmalonic aciduria were investigated.
  
  
  METHODS
  From 1996 to 2011, a total of 398 patients with methylmalonic aciduria were diagnosed in our hospital; 286 (71.9%) patients had early-onset before 1 year of age. Among 286 patients, 160 (55.9%) presented symptoms in neonatal period. Their urine organic acids were analyzed by gas chromatography-mass spectrometry. Blood amino acids and acylcarnitine profiles were determined by liquid chromatography tandem mass spectrometry. Serum and urine total homocysteine were measured using a fluorescence polarization immunoassay. In some patients, gene analysis was performed. Based on the disease types and general condition, individual dietary and medical interventions were started soon after diagnosis.
  
  
  RESULTS
  Out of the 160 patients, 131 (81.9%) had combined methylmalonic aciduria and homocysteinemia. Isolated methylmalonic aciduria was found in 29 cases (18.1%). The common presentations in neonatal period were feeding difficulty, seizures, lethargy and dyspnea. Megaloblastic anemia, liver dysfunction, hyperammonemia and metabolic acidosis were the frequent findings in the routine laboratory test. The most common initial clinical diagnosis was suspected hypoxic-ischemic encephalopathy. Even in 36 cases with abnormal family history, only 3 patients were admitted with suspected inborn errors of metabolism. Five cases (3.1%) were diagnosed by postmortem metabolic examination; 7 cases (4.4%) were detected by newborn screening. In 148 cases (92.5%), the diagnosis was much delayed to the age of one month to 8 years and 5 months (mean 13 months). Methylmalonic aciduria combined with homocysteinemia (MMACHC) gene analyses were performed in 31 cases with combined methylmalonic aciduria. CblC defect was confirmed. The patients with isolated methylmalonic aciduria were treated with protein-restricted diet, cobalamin and L-carnitine. The patients of methylmalonic aciduria combined with homocysteinemia were treated with cobalamin, L-carnitine, calcium folinate, betaine and common diet. Seven patients died without treatment. Clinical improvement was observed in 153 patients. Only 2 patients detected by newborn screening had normal mental and physical development. Mild to severe psychomotor retardation was observed in 151 cases.
  
  
  CONCLUSIONS
  High mortality and disability rates were observed in the patients with early-onset methylmalonic aciduria. Combined methylmalonic aciduria and homocysteinemia is the common type of methylmalonic aciduria. The clinical manifestation in neonatal period of the patients with early-onset methylmalonic aciduria is complex. Feeding difficulty, seizures, lethargy and dyspnea are the common symptoms in neonatal period of the patients. Megaloblastic anemia, liver dysfunction, hyperammonemia and metabolic acidosis were the frequent laboratory findings.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Yu-peng
authors.initials: YP
authors.lastname: Liu
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Ma
authors.forename: Tong-fei
authors.initials: TF
authors.lastname: Wu
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.forename: Xi-yuan
authors.initials: XY
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ding
authors.forename: Jin-qing
authors.initials: JQ
authors.lastname: Song
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Yan-ling
authors.initials: YL
authors.lastname: Yang
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D002331:Carnitine / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D008401:Gas Chromatography-Mass Spectrometry; D006710:Homocysteine / Q000097:blood / Q000652:urine; D006801:Humans; D020138:Hyperhomocysteinemia / Q000175:diagnosis* / Q000209:etiology / Q000628:therapy; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008764:Methylmalonic Acid / Q000652:urine*; D015997:Neonatal Screening; D012189:Retrospective Studies; D014805:Vitamin B 12 / Q000627:therapeutic use
chemical_list: D006710:Homocysteine; D008764:Methylmalonic Acid; D005492:Folic Acid; D014805:Vitamin B 12; D002331:Carnitine