Maple Syrup Urine Disease Carrier Test, DNA

CPT: 81205
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Test Details

Synonyms

  • BCKD Deficiency
  • Branched-chain Ketoaciduria
  • Jewish Heritage Test
  • MSUD Carrier Testing, DNA

Use

Carrier screening for Maple syrup urine disease (MSUD, OMIM 248600), an inherited recessive disease caused by deficient activity of branched-chain α-ketoacid dehydrogenase.

Limitations

The diagnosis of MSUD is made by the finding of alloisoleucine in plasma. DNA testing is appropriate for carrier screening in individuals of Ashkenazi Jewish or Mennonite ancestry, confirmation of mutations in patients previously diagnosed with MSUD who belong to these ethnic groups, and prenatal diagnosis for at-risk couples who are known to carry the mutations detected by this test. This DNA test only detects the Y438N, R183P, G278S, and E372X mutations found in the Ashkenazi Jewish and Mennonite populations. This test has limited value for individuals from other ethnic groups.

Methodology

Polymerase chain reaction (PCR) and primer extension

Additional Information

MSUD can be detected by newborn screening and effectively treated with dietary restriction.1,2 Almost all state newborn screening programs are required by statute to screen infants for MSUD.3 Untreated disease is characterized by poor feeding, brain damage, and ultimately coma and death. Even with dietary restriction of branched-chain amino acids, affected individuals may still have periodic metabolic crises due to infection or stress. Impaired intellectual development or neurological complications can occur if the initial diagnosis is delayed.2 The disease is present in all ethnic groups, but has elevated prevalence among Ashkenazi Jews and Mennonites.2,4 Parents who are each carriers of MSUD are asymptomatic, but have a 25% chance with each pregnancy to have a child with the disease. Prenatal diagnosis can be performed by molecular mutation analysis (when the mutations in the family are known) or by measurement of enzyme activity in amniocytes. Molecular testing for MSUD encompasses four mutations in two components of the branched-chain ketoacid dehydrogenase complex (BCKAD): the E1 α-subunit (BCKDHA, OMIM 608438), and the E1 β-subunit (BCKDHB, OMIM 248611). Plasma amino acid analysis can be used to diagnose affected individuals, but cannot determine carrier status. A negative result of this DNA test in an individual of Ashkenazi Jewish or Mennonite ancestry decreases the likelihood that a person is a carrier, but cannot completely eliminate the possibility. The presence of a rare mutation cannot be ruled out. DNA test results must be combined with clinical and family history information for the most accurate interpretation.

Specimen Requirements

Specimen

Whole blood, amniotic fluid, chorionic villus sample (CVS), or LabCorp buccal swab kit (buccal swab collection kit contains instructions for the use of a buccal swab)

Volume

7 mL whole blood, 10 mL amniotic fluid, 20 mg CVS, or LabCorp buccal swab kit

Minimum Volume

3 mL whole blood, 5 mL amniotic fluid, 10 mg CVS, or two buccal swabs

Container

Lavender-top (EDTA) tube, yellow-top (ACD) tube, sterile plastic conical tube or two confluent T-25 flasks for fetal testing, or LabCorp buccal swab kit

Storage Instructions

Maintain specimen at room temperature or refrigerate at 4°C.

Causes for Rejection

Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container; wet buccal swab

Clinical Information

Special Instructions

For the diagnosis of maple syrup urine disease, order Amino Acid Profile, Quantitative, Plasma [700068]. DNA testing is appropriate for carrier screening and confirmation of mutations in individuals from specific ethnic groups (see Limitations).

Footnotes

1. Strauss KA, Puffenberger EG, Morton DH. Maple syrup urine disease. available at: www.geneclinics.org. Accessed 2006.
2. Edelmann L, Wasserstein MP, Kornreich R, et al. Maple syrup urine disease: Identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population. Am J Hum Genet. 2001; 69(4):863-868.11509994
3. National Newborn Screening Status Report, National Newborn Screening and Genetics Resource Center. genes-r-us.uthscsa.edu, updated 12/17/2007.
4. Kornreich R, Edelmann L, Diaz GA, et al. High frequency of carrier for maple syrup urine disease in the Ashkenazi Jewish population. available at: www.ashg.org/cgi-bin/ashg04s/ashg04. Annual Meeting of the ASHG, 2004.

References

Monaghan KG, Feldman GL, Palomaki GE, et al, and the Ashkenazi Jewish Reproductive Screening Working Group; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee. Technical standards and guidelines for reproductive screening in the Ashkenazi Jewish population. Genet Med. 2008 Jan; 10(1):57-72.18197058

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
511310 MSUD, Carrier Testing, DNA 511368 Maple Syrup Urine Disease 53039-4
511310 MSUD, Carrier Testing, DNA 511954 PDF 51969-4
511310 MSUD, Carrier Testing, DNA 511005 Jewish Heritage Putaway N/A

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