Hydroxymethylglutaric aciduria

Alternative names
  • 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
  • HMG-CoA lyase deficiency
About the condition Hydroxymethylglutaric aciduria is an organic acid disorder. It is a hereditary disease that is caused by a missing enzyme needed to convert protein into energy. There is also failure to produce ketone bodies.
Inheritance Autosomal recessive
Year screening started in WA
2005 
Incidence in Australia Currently unknown
Enzyme defect Deficiency of HMG-CoA lyase, which catalyses the final step of leucine degradation and plays a role in ketone formation.
Symptoms if untreated
  • Hypoketotic hypoglycaemia
  • Metabolic acidosis
  • Vomiting
  • Lethargy, hypotonia
  • Apnoea, seizures
  • Hepatomegaly
  • Coma and death possible
Metabolites on bloodspot screening Increased hydroxymethylglutarylcarnitine (C5MeDC) and hydroxyisovalerylcarnitine (C5OH).
Diagnostic tests
  • Plasma acylcarnitine profile
  • Urine organic acids
  • HMGCL gene analysis
Treatment
  • High-carbohydrate, low-protein diet
  • Carnitine supplementation
  • Avoidance of fasting
  • IV glucose during crisis episodes
Screening issues None