GeneDx :: Tests :: HMG CoA Lyase Deficiency (3-Hydroxy-3-Methylglutaryl CoA Lyase Deficiency)

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HMG CoA Lyase Deficiency (3-Hydroxy-3-Methylglutaryl CoA Lyase Deficiency)

HMGCL gene

3-Hydroxy-3-methylglutaryl CoA lyase deficiency, commonly known as HMG CoA lyase deficiency, is a rare inborn error that affects ketogenesis and leucine catabolism. Symptoms usually appear in the first year of life and include metabolic acidosis with hypoketotic hypoglycemia, hyperammonemia, abnormal liver function tests, vomiting and hypotonia. Other signs are hepatomegaly, macrocephaly, and less frequently microcephaly, seizures, acute pancreatitis, dilated cardiomyopathy and arrhythmia. Brain MRI can show abnormal cerebral white matter foci. This disorder is fatal in approximately 20% of cases. Without treatment, rapid progression to coma and death or permanent neurological damage may occur. With treatment, many patients do well; however recurrent metabolic decompensation continues to occur especially with prolonged fasting or intercurrent illness. The symptoms become milder after childhood.

Using genomic DNA obtained from blood (2mL for infants, 5mL for adults in EDTA) or buccal swabs (not accepted on infants), mutation analysis of the HMGCL gene is performed. GeneDx offers the option of first testing for mutations in exon 2 where the c.122 G>A mutation (common in Saudi Arabian patients) and the c.109 G>A mutation (common in patients from Spain and Portugal) are located. Sequencing of exon 2 is predicted to identify both mutations in approximately 86% of Saudi Arabian patients and in approximately 67% of Portuguese patients. If the patient is not from Saudi Arabian, Portuguese or Spanish ancestry, or if homozygosity for these mutations is not observed, sequencing of the entire coding sequence and intron/exon boundaries of the HMGCL gene should be ordered. Carrier testing and prenatal diagnosis is available once the mutation in the family has been defined.

Information Sheet, including prices and CPT codes
Consent Document
Genetic Test Sample Submission Form (Test Requisition Form) including Payment Options

HL DEFICIENCY, HYDROXYMETHYLGLUTARIC ACIDURIA, LEUCINE METABOLISM, 3-hydroxy-3-methylglutaric, 3-hydroxyisovaleric, 3-methyl-glutaconic and 3-methylglutaric acids, 3-methylcrotonylglycine, HMG-CoA Lyase deficiency, newborn screening