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.