Mutations in DLD are responsible for a very rare variant form of the recessive condition maple syrup urine disease (MSUD). MSUD type III (or E3 deficient MSUD) initially presents in newborns with symptoms common to intermediate MSUD, but also includes severe lactic acidosis, which is potentially life-threatening. Persistant lactic acidosis occurs between eight weeks and six months of life. In addition to lactic acidosis, patients with E3-deficient MSUD can display neurologic deterioration, hypotonia, developmental delay, and movement disorders. Laboratory findings include elevated blood pyruvate, lactate, alpha-ketoglutarate, branched-chain amnio acids, alpha-hydroxyisovalerate, and alpha-hydroxyglutarate. Dietary therapy, vitamin therapy with thiamine and biotin, and lipoic acid therapy have all been attempted without success.
Sequencing of the DLD gene is recommended after a biochemical diagnosis of E3-deficient MSUD, and provides a complementary method to confirm the presence of mutations in a proband, identify carriers among the proband's relatives, and provide prenatal diagnosis in families with known mutations.
For patients with mutations not identified by full gene sequencing, a separate deletion/duplication assay is available using a targeted CGH array (HJ).
- Confirmation of a clinical/biochemical diagnosis of E3-deficient MSUD
- Carrier testing in adults with a family history of E3-deficient MSUD
Analytical Sensitivity: ~99%
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple 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.
- Plasma Amino Acid Analysis (AA)
- Urine Organic Acid Analysis (OA)
- Custom Diagnostic Mutation Analysis (KM) is available to family members if mutations are identified by sequencing.
- 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.