HMG-CoA lyase deficiency is a condition where the body lacks an enzyme needed to break down a specific amino acid called leucine, which is essential for building proteins. People with this condition also can’t produce ketones, an important energy source used when fasting or sick.
Symptoms usually start before a child turns one, showing up as episodes known as “metabolic crises.” During these times, the child might have low blood sugar, vomiting, lack of energy, and floppy muscles. These crises can be triggered by illness, fasting, stress, or high protein intake. If not treated with a special diet, these episodes can lead to serious complications like neurological damage, coma, or even death. Treatment involves avoiding fasting, following a low-leucine diet, taking medications, and being vigilant during metabolic crises. Special diets are necessary, sometimes requiring constant eating, even at night. A “sick day plan” is created for times of illness, emphasizing frequent carbohydrate-rich meals and increased fluid intake. During illness, fats and proteins are removed from the diet.
HMG-CoA lyase deficiency is caused by pathogenic (disease-causing) variants in the HMGCL gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background.
Other names for this condition are 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency, 3-OH 3-methyl glutaric aciduria, deficiency of hydroxymethylglutaryl-CoA lyase, HMG-CoA lyase deficiency, and hydroxymethylglutaric aciduria.