The ACAD8 gene (11q25) encodes isobutyryl Co-A dehydrogenase, which catalyzes the third step of the degradation of the branched chain amino acid valine [6,7]. ACAD8 is a member of the Acyl-coenzyme A (CoA) dehydrogenases (ACADs) family of mitochondrial enzymes that catalyze the first dehydrogenation step in the beta-oxidation of fatty acyl-CoA derivatives . Fatty acids provide important respiratory fuel for many tissues, including heart, skeletal muscle, brown adipose tissue, kidney, and liver, as is evident in individuals with defects in any of the ACAD family members. The mitochondrial beta-oxidation pathway is a cycle of 4 sequential reactions in which the fatty acid substrate is shortened by 2 carbon atoms with each cycle, releasing an acetyl-CoA molecule that can then be used in the tricarboxylic acid cycle or for ketogenesis.
- 1. Roe et al. Isolated isobutyryl-CoA dehydrogenase deficiency: an unrecognized defect in human valine metabolism. Molec. Genet. Metab. 1998, 65:264-271.
- 2. Oglesbee et al. Development of a newborn screening follow-up algorithm for the diagnosis of isobutyryl-CoA dehydrogenase deficiency. Genet. Med. 2007, 9: 108-116.
- 3. Koeberl et al. Rare disorders of metabolism with elevated butyryl- and isobutyryl-carnitine detected by tandem mass spectrometry newborn screening. Pediat. Res. 2003, 54: 219-223.
- 4. Sass et al. Isobutyryl-CoA dehydrogenase deficiency: isobutyrylglycinuria and ACAD8 gene mutations in two infants. J. Inherit. Metab. Dis. 2004, 27: 741-745.
- 5. Pedersen et al. Variations in IBD (ACAD8) in children with elevated C4-carnitine detected by tandem mass spectrometry newborn screening. Pediat. Res. 2006, 60: 315-320.
- 6. Nguyen et al. Identification of isobutyryl-CoA dehydrogenase and its deficiency in humans. Molec. Genet. Metab. 2002, 77: 68-79.
- 7. Telford et al. Isolation and characterisation of a cDNA encoding the precursor for a novel member of the acyl-CoA dehydrogenase gene family. Biochim. Biophys. Acta 1999, 1446: 371-376.
This test is indicated for:
- Confirmation of a clinical diagnosis of IBD deficiency in individuals who have tested negative for sequence analysis
- Carrier testing in adults with a family history of IBD deficiency who have tested negative for sequence analysis
Please note that a "backbone" of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off-target copy number variants causative of disease may be identified that may or may not be related to the patient's phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.
Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple top) or ACD (yellow top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
Specimen Requirements:OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.
Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of Emory Genetics Laboratory, please submit a copy of the sequencing report with the test requisition.
- Sequence analysis of the ACAD8 gene is available and is required before deletion/duplication analysis.
- Prenatal testing is available to couples who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.