Biochemical, molecular and outcome analysis of eight chinese asymptomatic individuals with methyl malonic acidemia detected through newborn screening

Am J Med Genet A. 2015 Oct;167A(10):2300-5. doi: 10.1002/ajmg.a.37147. Epub 2015 May 17.

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.

Keywords: asymptomatic; methyl malonic academia; methyl malonic acid; new born screening.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcarnitine / blood
  • Acidosis / blood
  • Acidosis / diagnosis
  • Acidosis / ethnology
  • Acidosis / genetics*
  • Asian People
  • Asymptomatic Diseases
  • Carboxy-Lyases / blood
  • Carboxy-Lyases / deficiency*
  • Carboxy-Lyases / genetics
  • Carnitine / analogs & derivatives
  • Carnitine / blood
  • Carrier Proteins / genetics*
  • Child
  • Citrates / urine
  • Female
  • Gene Expression
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Malonates / blood*
  • Malonates / urine
  • Malonyl Coenzyme A / blood
  • Malonyl Coenzyme A / genetics
  • Metabolism, Inborn Errors / blood
  • Metabolism, Inborn Errors / diagnosis
  • Metabolism, Inborn Errors / ethnology
  • Metabolism, Inborn Errors / genetics*
  • Methylmalonic Acid / blood
  • Methylmalonyl-CoA Mutase / genetics*
  • Mutation
  • Neonatal Screening
  • Oxidoreductases

Substances

  • Carrier Proteins
  • Citrates
  • Malonates
  • propionylcarnitine
  • Malonyl Coenzyme A
  • 2-methylcitric acid
  • Acetylcarnitine
  • Methylmalonic Acid
  • MMACHC protein, human
  • Oxidoreductases
  • Carboxy-Lyases
  • Methylmalonyl-CoA Mutase
  • methyl malonate
  • Carnitine

Supplementary concepts

  • Malonic aciduria