Multiple carboxylase deficiency (MCD)

Alternative name Holocarboxylase synthetase (HCS) deficiency
About the condition MCD is an organic acid disorder. It is a hereditary disease that is caused by a missing enzyme needed to convert protein into energy.
Inheritance Autosomal recessive
Year screening started in WA
2005
Incidence in Australia Currently unknown
Enzyme defect Deficiency of holocarboxylase synthetase, the enzyme that covalently links biotin to three carboxylases: propionyl-CoA carboxylase, pyruvate carboxylase, and 3-methylcrotonyl-CoA carboxylase.
Symptoms if untreated
  • Metabolic ketolactic acidosis
  • Vomiting, lethargy
  • Seizures, hypotonia
  • Skin rashes, hair loss
  • Hearing loss, optic atrophy
  • Recurrent infections
  • Intellectual disability
  • Coma and death possible
  • Later-onset forms occur
Metabolites on bloodspot screening
  • Increased propionylcarnitine (C3) and hydroxyisovalerylcarnitine (C5OH)
  • Increased methylcitrate (second-tier test)
Diagnostic tests
  • Plasma acylcarnitine profile
  • Urine organic acids
  • HLCS gene analysis
Treatment Biotin supplementation
Screening issues Biotinidase deficiency is not detected by this screening strategy.