Methylmalonic aciduria

Alternative names
  • Methylmalonyl-CoA mutase deficiency
  • Cbl A, Cbl B, Cbl C, Cbl D
About the condition MMA is an organic acid disorder. It is a hereditary disease that is caused by a missing enzyme needed to convert protein into energy. The disorder can also result from deficiency of the cobalamin cofactor required by the mutase enzyme.
Inheritance Autosomal recessive
Year screening started in WA
Incidence in Australia Approximately 1 in 75,000 births
Enzyme defect
  • Defect in methymalonyl-CoA mutase or synthesis of its adenosylcobalamin cofactor
  • At least five distinct biochemical causes of this disorder have been identified
Symptoms if untreated
  • Episodic ketoacidosis
  • Hyperammonaemia
  • Vomiting, FTT
  • Seizures, intellectual disability
  • Coma and death possible
  • Later-onset and milder forms occur
Metabolites on bloodspot screening
  • Increased propionylcarnitine (C3)
  • Increased methylmalonate (second-tier test)
Diagnostic tests
  • Plasma acylcarnitine profile
  • Urine organic acids
  • Plasma MMA and total homocysteine
  • Vitamin B12
  • MMA gene panel
  • Low-protein diet
  • Vitamin B12 for responsive forms
  • Carnitine supplementation
  • More intensive treatment during acute crises
Screening issues
  • Screening will detect mutase deficiency, Cbl A, B, C and D forms.
  • Later-onset and milder variants may not be detected