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LCHAD/Trifunctional Protein Deficiency HADHA Full Sequencing

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.

Sequencing of the HADHA gene is recommended for patients with a biochemical diagnosis of LCHAD or TFP deficiency, to provide molecular confirmation of the diagnosis. The most common mutation in isolated LCHAD deficiency is the E510Q (c. 1528G>C) mutation, accounting for 87% of alleles.

Test Name: LCHAD/TFP (HADHA) Sequencing Analysis
Test Code:
LCHAD SEQ
Test Description:
Polymerase Chain Reaction (PCR) followed by sequence analysis of the entire coding region (20 exons) of the HADHA gene.
Synonyms:
MTP, mitochondrial trifunctional protein, long chain, LCHAD TFP
Indication:
This test is used to provide additional information regarding diagnosed patients or as a secondary confirmation of diagnosis. Sequencing can also be used for carrier testing.
Related Tests: Organic Acid Analysis, Urine  
For confirmation of newborn screening results, evaluating patients with episodes of lethargy or vomiting suggestive of a metabolic disorder and for follow-up of known patients for assessment of management.

Acylcarnitine Profile, Blood  
For confirmation of newborn screening results, evaluating patients with episodes of lethargy or vomiting suggestive of a metabolic disorder and for follow-up of known patients for assessment of management.

LCHAD/TFP (HADHB) Sequencing Analysis  
This test is used to provide additional information regarding diagnosed patients or as a secondary confirmation of diagnosis. Sequencing can also be used for carrier testing.

LCHAD/TFP (HADHA) Known Mutation Analysis  
This test is used for carrier testing at-risk relatives and prenatal testing for confirmed carriers. Mutations must be known.

Clinical Links: LCHAD E-Medicine Review Article
LCHAD OMIM Entry
Trifunctional Protein Deficiency OMIM Entry
Availability:
Mon - Fri
Turnaround Time:
2-3 weeks
Methodology:
PCR followed by Sequencing
Reference Range:
Interpretive report will be provided
Requisition:
Consent Form:
Sample Requirements: Type
Whole blood: 1-3 mL in EDTA (purple top) or ACD (yellow top). DNA: 5 micrograms extracted DNA.

Processing
Do not spin. Refrigerate blood samples which will not be immediately shipped.

Shipping
Room temperature via overnight shipping.
Samples Received:
Monday - Friday 8am - 5pm PST
Special Considerations:
Cost:
Please e-mail Lab Client Services (labclientservices@seattlechildrens.org) or call at 206-987-2617 with any billing questions
CPT Code:
Please e-mail Lab Client Services (labclientservices@seattlechildrens.org) or call at 206-987-2617 with any billing questions