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 |
Variants | No |
Variant name | N/A |
Symptom onset | Infancy (6 months to 2 years) |
Symptoms | Persistent vomiting, lethargy, hypotonia, coma, seizures, apnea, hepatomegaly. |
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 |
Inheritance | Autosomal recessive |
General population incidence | Rare |
Ethnic differences | No |
Population | N/A |
Ethnic incidence | N/A |
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. |
Gene | HMGCL |
Gene location | 1pter-p33 |
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 method. |
MS/MS Profile | N/A |
OMIM Link | www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=246450 |
Genetests Link | www.genetests.org |
Support Group | Organic Acidemia Association Save Babies through Screening Foundation |