A neonatal case of 3-hydroxy-3-methylglutaric-coenzyme A lyase deficiency

Ital J Pediatr. 2013 May 24:39:33. doi: 10.1186/1824-7288-39-33.


3-hydroxy-3-methylglutaric aciduria (OMIM 246450) is a rare autosomal recessive inborn of metabolism due to the deficiency of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase, an enzyme involved both in the ketogenic pathway and leucine catabolism. Acute decompensations present with lethargy, cianosis, hypotonia, vomiting and metabolic acidosis with hypoketotic hypoglycemia. We report the case of a 3 days male with sudden hypoglycemic crisis initially misdiagnosed as a sepsis. HMG-CoA lyase deficiency was achieved through acyl-carnitines profile (showing a typical increasing of 3-hydroxy-isovaleryl and 3-methylgluraryl carnitines) and urinary organic acids analysis (disclosing elevation of 3-hydroxy-3-methylglutaric, 3-methyl-glutaconic, 3-methylglutaric and 3-hydroxyisovaleric acids). This case underlines the need of suspecting such inborn metabolic disorder in cases with hypoglycemia and metabolic acidosis. Acyl-carnitine and urinary organic acids profiles are essential to achieve a prompt diagnosis of treatable metabolic disorders in order to prevent their acute crisis with serious or even fatal consequences.

Publication types

  • Case Reports

MeSH terms

  • Acetyl-CoA C-Acetyltransferase / deficiency*
  • Acidosis / etiology
  • Acute Disease
  • Amino Acid Metabolism, Inborn Errors / diagnosis*
  • Glutarates / urine
  • Glycine / analogs & derivatives
  • Glycine / urine
  • Humans
  • Hypoglycemia / etiology
  • Infant, Newborn
  • Male
  • Meglutol / analogs & derivatives
  • Meglutol / urine


  • Glutarates
  • beta-methylcrotonylglycine
  • 3-methylglutaric acid
  • 3-methylglutaconic acid
  • Meglutol
  • Acetyl-CoA C-Acetyltransferase
  • Glycine

Supplementary concepts

  • 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency