Also known as: 3-hydroxy-3-methylglutaryl-CoA lyase deficiency,3-HMG-CoA lyase deficiency, HMGCLD


1. The disease

A rare organic aciduria, due to deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase characterized by episodes of metabolic decompensation with hypoketotic hypoglycemia triggered by periods of fasting or infections. This conditions is extremely rare in the United States, Taiwan and China where incidence is estimated at less than 1/1,000,000; however, it is more frequently observed in Saudi Arabia, Portugal and Spain, with an estimated prevalence of 1/125,000 live births.

2. The symptoms

The clinical presentation is heterogeneous, ranging from severe neonatal onset with potentially fatal outcome to first symptoms in adulthood. Most patients became symptomatic within the first year of life (50% in neonatal period) with episodes of metabolic decompensation triggered by periods of fasting, dietary changes, vaccination or infections, which when left untreated may lead to neurological sequelae. Newborns or infants present with acidosis and hypoglycemia, accompanied by vomiting, dehydration, hypotonia and lethargy. The typical laboratory findings include hypoglycemia, acidosis, an increased anion gap, hyperammonemia and elevated transaminases. Long-term neurological complications are common. Half of the patients have a normal cognitive development while the remainder shows psychomotor deficits. Speech and motor developmental delay are frequent. Children are usually healthy between episodes. Lack of early signs or symptoms does not exclude the diagnosis.

3. Actions to take in case of early diagnosis

  • Infants with a positive genetic test should continue breastfeeding and AVOID FASTING. Early treatment, with frequent fractional meals/ frequent breastfeeding, is essential in preventing chronic symptoms. L-carnitine supplementation can help.
  • Biochemical correlation is essential for confirming diagnosis with tandem mass spectrometry – increase of C5-OH and C6-DC metabolytes in blood or filter paper.
  • HMGCLD is a lifelong disease that requires lifetime management and regular follow-up with a metabolic physician and a multidisciplinary approach to care.
  • Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.


4.    More informations