Maple Syrup Urine Disease (MSUD) Carrier Testing, DNA

Maple Syrup Urine Disease (MSUD) Carrier Testing, DNA

Number
	511310
CPT
	83891; 83892; 83900; 83901 (x2); 83912; 83914 (x4)
Synonyms
	BCKD Deficiency ; Jewish Heritage Test ; Branched-Chain Ketoaciduria ; MSUD, Carrier Testing, DNA
Special Instructions
	***Note: For diagnosis and treatment monitoring of MSUD order test Amino Acid Profile, Quantitative, Plasma [095638]. DNA testing is appropriate for carrier screening and confirmation of mutations in individuals from specific ethnic groups (see Clinical Limitations).
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, 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 or hemolyzed specimen; quantity not sufficient for analysis; improper container; wet buccal swab
Use
	Maple syrup urine disease (MSUD, OMIM 248600) is an inherited recessive disease caused by deficient activity of branched-chain alpha-ketoacid dehydrogenase.
Limitations
	The diagnosis of MSUD is made by the finding of allo-isoleucine 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. This procedure may be considered by Medicare and other carriers as investigational and therefore, may not be payable as a covered benefit for patients.
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 amnio 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 asympomatic, 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 alpha subunit (BCKDHA, OMIM 608438), and the E1 beta 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.
Footnotes
	1. Strauss KA, Puffenberger EG, Morton DH. Maple syrup urine disease. www.geneclinics.org 2006. 2. Edelmann L, Wasserstein MP, Kornreich R, Sansarieq C, Snyderman SE, Diaz GA. Maple syrup urine disease: Identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population. Am J Hum Genet. 2001; 69:863-868. 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, Desnick RJ. High frequency of carrier for maple syrup urine disease in the Ashkenazi Jewish population [abstract] www.ashg.org/cgi-bin/ashg04s/ashg04. Annual Meeting of the ASHG; 2004.