3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase) deficiency
HMG-CoA lyase deficiency is inherited in an autosomal recessive pattern. Normally a person has two functional HMGCL genes. In people with HMG-CoA lyase deficiency, both genes have a mutation and there is a deficiency of the critical enzyme activity. Each parent of a newborn with HMG-CoA lyase deficiency typically has one functional and one mutated gene and is considered a carrier. When both parents are carriers, the chance of a newborn inheriting two mutated genes is 25%.
None known
The age of onset of symptoms varies from the first 5 days of life (30%), the first year of life or as late as adulthood (very rarely). The symptoms may include vomiting, low muscle tone, lethargy and coma. Blood tests show hypoglycemia (low blood sugar), elevated lactate and low ketones (produced when the body uses fats for energy). Symptoms may be caused by an illness or fasting. Some patients are inaccurately diagnosed with Reye syndrome.
Some patients will recover completely from their first episode, but others will have neurological symptoms including seizures and intellectual disability.
There are reports of people with HMG-CoA lyase deficiency that never develop symptoms.
- Incidence: HMG-CoA lyase deficiency is very rare. It is more common in people from Saudi Arabia.
- New York State Method of Screening (First Tier): Screening for HMG-CoA lyase deficiency is accomplished by measuring the acylcarnitine C5OH by tandem mass spectrometry (MS/MS).
- Second Tier Screening: None
- Testing can be affected by: Newborn screening cannot distinguish between HMG-CoA lyase deficiency and other disorders with elevated C5OH (3-MCC, 3-MGA and BKT deficiencies).
- Interpretation/reporting of data: Results are reported as screen negative, borderline or as a referral. A repeat specimen should be collected for a borderline result. Prompt consultation with a specialist is required for a referral.
- Referral to Specialty Care Center: Patients with an abnormal newborn screen for HMG-CoA lyase deficiency are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of HMG-CoA lyase deficiency.
Diagnostic testing may include urine organic acid analysis, plasma acylcarnitine analysis, HMGCL gene sequencing and enzyme analysis in fibroblasts.
Treatment is typically dietary management, including careful monitoring of fat, protein and carbohydrate intake. Additional medical care, including admission to the hospital for intravenous feedings, may be required during times of illness.
Some patients completely recover from their first episode, but others continue to have neurological symptoms.
3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase) deficiency is a disorder of organic acid metabolism (inherited metabolic disorder).
A component of protein (leucine) is broken down as part of the normal metabolism of fatty acids for energy. The HMGCL gene provides instructions for an important enzyme in this process. If there is a mutation in HMGCL gene, the enzyme does not function, leucine builds up and fatty acids cannot be used for energy. Toxic metabolites also accumulate and may cause symptoms.