3-Hydroxy-3-MethylGlutaryl-CoA Lyase Deficiency via the HMGCL Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
9653 HMGCL 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9653HMGCL81479 81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

3-hydroxy-3-methylglutaryl (HMG)-CoA lyase deficiency (OMIM 246450) is a rare defect in the last step in leucine catabolism. The defect also affects breakdown of fatty acids and reduces production of ketone bodies. Typically, the disorder is diagnosed in infants with symptoms of vomiting, lethargy, hepatomegaly, and seizures. The disorder can be lethal. During disease episodes, children develop hypoketotic hypoglycemia, hyperammonemia, and acidosis. HMG-CoA lyase deficiency has also been diagnosed in adults with leukoencephalopathy (Bischof et al. Ann Neurol 56:727- 730, 2004). The disease may lead to lifelong learning problems and mental retardation. These days, many cases are detected through routine neonatal screening with tandem mass spectrometry.

Genetics

3-hydroxy-3-methylglutaryl (HMG)-CoA lyase deficiency is an autosomal recessive disease. The enzyme is encoded by the HMGCL gene on chromosome 1p36. About 40 causative HMGCL variants have been reported. They are missense, nonsense, splicing, and frameshift. A few larger deletions that would not be detectable by DNA sequencing have been reported (see for example Muroi et al. Hum Genet 107:320-6, 2000). The disorder appears to be particularly common in Saudi Arabia (Al-Sayed et al. BMC Med Genet 7:86, 2006) and Portugal.

Testing Strategy

This test provides full coverage of all coding exons of the HMGCL gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Clinical Sensitivity - Sequencing with CNV PGxome

Sensitivity of this test for patients diagnosed by biochemistry should be high.

Indications for Test

All HMG-CoA lyase deficiency patients and their family members are candidates for this test. PreventionGenetics offers testing for many other neonatal screening disorders. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in HMGCL.

Gene

Official Gene Symbol OMIM ID
HMGCL 613898
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency AR 246450

Citations

  • Al-Sayed, M., et.al. (2006). "Mutations underlying 3-hydroxy-3-methylglutaryl CoA lyase deficiency in the Saudi population." BMC Med Genet 7: 86. PubMed ID: 17173698
  • Bischof, F., et.al. (2004). "3-hydroxy-3-methylglutaryl-CoA lyase deficiency in an adult with leukoencephalopathy." Ann Neurol 56(5): 727-30. PubMed ID: 15505778
  • Muroi, J., et.al. (2000). "Molecular and clinical analysis of Japanese patients with 3-hydroxy-3-methylglutaryl CoA lyase (HL) deficiency." Hum Genet 107(4): 320-6. PubMed ID: 11129331

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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