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.
- Confirmation of a clinical/biochemical diagnosis of E3-deficient MSUD
- Carrier testing in adults with a family history of E3-deficient MSUD
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.
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.