TRIFUNCTIONAL PROTEIN DEFICIENCY

HADHB encodes the beta subunit of Hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, or trifunctional protein. This enzyme is a heteromeric complex consisting of 4 alpha and 4 beta subunits that catalyzes 3 steps in the beta-oxidation of fatty acids. The alpha subunit has activities of the long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD)/enoyl-CoA hydratase; the beta subunit harbours the 3-ketoacyl-CoA thiolase activity. Mutations in the HADHB gene have been reported in the patients with trifunctional protein deficiency in whom all 3 enzymatic activities are low. Three forms of HADHB deficiency have been described:

• Lethal: a rapidly progressive severe neonatal presentation with cardiomyopathy, Reye-like syndrome, and neonatal demise
• Hepatic: with recurrent hypoketotic hypoglycaemia
• Myopathic: with a milder later-onset neuromyopathy and episodic myoglobinuria.

Maternal HELLP may be present regardless of the fetal phenotype. The human HADHB gene is located in the chromosome 2p23.3 and consists of 16 exons encoding 474 amino acid residues.

Reasons for Referral:

• Confirmation of a clinical diagnosis
• Carrier testing

Testing Methodology:

The exons and flanking intronic regions of the HADHB gene are PCR amplified and sequenced in both the forward and reverse directions.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult: 14 cc; Child: 6 cc; Infant: 2-3 cc
Requisition form must accompany the specimen. To receive forms, additional information or specimen collection kits, please contact the laboratory.

Turnaround Time:

Index: 4 weeks
Known Familial Mutation: 2 weeks

CPT Codes and Prices:

Index: 83912, 83894, 83891, 83898x13, 83904x26, 83909x26
Known Familial Mutation: 83912, 83894, 83891, 83898, 83904x2, 83909x2

Shipping Information

Forms:

>> Molecular Diagnostic Requisition

References:

1. Ushikubo S, Aoyama T, Kamijo T, Wanders RJA, Rinaldo P, Vockley J, Hashimoto T. Molecular characterization of mitochondrial trifunctional protein deficiency: formation of the enzyme complex is important for stabilization of both alpha- and beta-subunits. Am. J. Hum. Genet. 58: 979-988, 1996.
2. Orii KE, Aoyama T, Wakui K, Fukushima Y, Miyajima H, Yamaguchi S, Orii T, Kondo N, Hashimoto T. Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency. Hum. Mol. Genet. 6: 1215-1224, 1997.
3. Spiekerkoetter U, Sun B, Khuchua Z, Bennett MJ, Strauss AW. Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to beta-subunit mutations. Hum. Mutat. 21: 598-607, 2003.

Test Codes:

Index: 3630
Known Familial Mutation: 3631

Medical Genetics Laboratories
Baylor College of Medicine · Houston, TX 77030
Phone: 1-800-411-GENE · Fax: 713-798-2787
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