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Test Code LCHAD KNWN LCHAD Known Mutation

Clinical System Name

LCHAD/TFP Known Mutation Analysis

Synonyms

HADHA

HADHB

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

Description

This test involves targeted analysis for variants previously identified through clinical testing of a family member or  research testing of the individual.  It can be used for carrier testing for at-risk relatives and prenatal testing for confirmed carriers. Variants must be known.  For full gene sequencing of HADHA or HADHB please see LCHAD Sequencing.

Sample Requirements

Specimen: Whole blood, cord blood

Container(s): Lavender/EDTA, Yellow/ACD A or B

Preferred Vol: 3 mL

Minimum Vol: 1 mL

 

Note: Heparin samples (Green tops) are unacceptable.

 

Specimen: Extracted DNA

Minimum: 10µg

Note: DNA concentration minimum 50 µg/mL; 260/280 ratio 1.70-2.00

  

Specimen: Cultured cells

Acceptable:  Fibroblasts

Container(s): T-25 flasks

Preferred Vol: 2 flasks

Processing Instructions

Reject due to: Heparin

Spin: No

Aliquot: No

Temp: Refrigerate

Storage location: Molecular Genetics box in CPA refrigerator #2

 

Off-site collection: Refrigerate blood samples until ready to ship.  Transport all sample types at room temperature via overnight shipping.

Stability

Specimen Type Temperature Time
Cultured cells Room temp 3 days
Whole blood, extracted DNA Room temp 3-5 days
Whole blood, extracted DNA Refrigerated 7 days
Extracted DNA Frozen ok

 

Note: Whole blood samples > 7days may be submitted to be assessed by our lab for acceptability for testing.

Availability

STAT Performed TAT
Contact lab Monday - Friday 2-3 weeks

 

Performing Laboratory

Seattle Children's Laboratory

Department

Department:  Molecular Genetics Laboratory

Phone: 206-987-3872

 

Lab Client Services: 206-987-2617

 

Lab Genetic Counselors: LabGC@seattlechildrens.org

Reference Range

Interpretive report will be provided

Methodology

Method: PCR + Sequencing

 

Limitations: This test is for targeted known mutation analysis only.  Mutations must be known

CPT Codes

HADHA 81403, HADHB 81479   (updated 1/27/16 by dstern)

Special Instructions

Please provide copies of proband reports when requesting known mutation analysis for cases NOT performed by Seattle Children's Lab.

 

Links to:  LCHAD E-Medicine Review Article; LCHAD OMIM Entry; Trifunctional Protein Deficiency OMIM Entry

Requisition

Molecular Genetics

Clinical Utility

Long-chain-hydroxy Acyl-CoA dehydrogenase deficiency (LCHAD), and mitochondrial trifunctional protein deficiency (TFP) are disorders of long-chain fatty acid metabolism. They have overlapping clinical presentation that can include: feeding difficulties, lethargy, hypoglycemia, muscle weakness and liver dysfunction in infancy or early childhood. These symptoms are often triggered by prolonged fasting or viral infections. Muscle pain, breakdown of muscle tissue and peripheral neuropathy may occur later in childhood. These patients are at risk for complications such as life-threatening heart problems and sudden unexpected death. Carrier women pregnant with affected fetuses can develop Acute Fatty Liver of Pregnancy (AFLP).

The mitochondrial trifunctional protein consists of 3 enzymes that work together to metabolize long-chain fats. Most patients have isolated deficiency of the LCHAD enzyme caused by mutations in the HADHA gene. A small portion of patients have defects in all three enzymes, called TFP deficiency, which is due to mutations in the HADHA or HADHB gene.

 

The most common pathogenic variant in isolated LCHAD deficiency is the p.E510Q (c.1528G>C) variant, accounting for an allele frequency of 87% in LCHAD deficient patients.