Organic Acid Disorders
|Disease Name||3-hydroxy-3-methylglutaryl-CoA lyase deficiency|
|Alternate name(s)||Hydroxymethylglutaric aciduria|
|Acronym||HMG-CoA lyase deficiency|
|Disease Classification||Organic Acid Disorder|
|Symptom onset||Infancy (6 months to 2 years)|
|Symptoms||Persistent vomiting, lethargy, hypotonia, coma, seizures, apnea,
|Natural history without treatment||Recurrent episodes of acute illness usually in response to fasting
or to viral infection. Any episode can lead to death or
developmental delay if severe enough.
|Natural history with treatment||Normal IQ and development are possible. Severe hypoglycemic episodes may result in seizures and mental retardation.|
|Treatment|| Avoidance of fasting. Low fat, protein and high carbohydrate diet.
Cornstarch supplementation. Carnitine supplementation.
Intravenous glucose to treat hypoglycemia during crisis episodes.
|Other||Crises consist of severe acidosis and hypoglycemia treated with IV glucose and bicarbonate administration.|
|Physical phenotype||Possible microcephaly|
|General population incidence||Rare|
|Enzyme location||Liver, fibroblasts and leukocytes|
|Enzyme Function||Catalyzes the final step of leucine degradation and plays a role in ketone formation.|
|Missing Enzyme||HMG CoA lyase|
|Metabolite changes||3-hydroxy-3-methylglutaric acid in urine, increased levels of
glutaric and adipic acids may be elevated in urine during crisis,
notable absence of ketosis.
|DNA testing available||No|
|DNA testing detail||N/A|
|Prenatal testing|| Prenatal testing has been accomplished by analysis of
metabolites in maternal urine at 23 weeks. Enzyme is active in
amniocytes and prenatal testing should be possible using this
Organic Acidemia Association