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Test ID MSUDP Maple Syrup Urine Disease Gene Panel, Varies

Ordering Guidance

The recommended first-tier screening tests for maple syrup urine disease (MSUD) are a combination of biochemical tests including quantitative plasma amino acids and urine organic acids. Order AAQP / Amino Acids, Quantitative, Plasma and OAU / Organic Acids Screen, Urine.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

Specimen Type: Whole blood


Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated


1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing  (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions

Useful For

Follow up for abnormal biochemical results suggestive of maple syrup urine disease (MSUD)


Establishing a molecular diagnosis for patients with MSUD


Identifying variants within genes known to be associated with MSUD, allowing for predictive testing of at-risk family members

Method Name

Custom Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.

Reporting Name

MSUD Gene Panel

Specimen Type


Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Clinical Information

Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by the deficiency of the branched-chain ketoacid dehydrogenase (BCKDH) complex. The BCKDH complex is involved in the metabolism of the branched-chain amino acids (BCAA): isoleucine (Ile), leucine (Leu), and valine (Val).


MSUD can be divided into 5 phenotypes: classic, intermediate, intermittent, thiamine-responsive, and dihydrolipoyl dehydrogenase (E3)-deficient, depending on the clinical presentation and response to thiamine administration. Classic MSUD, the most common and most severe form, presents in newborns with feeding intolerance, failure to thrive, vomiting, lethargy, and maple syrup odor in urine and cerumen. If untreated, it progresses to irreversible mental retardation, hyperactivity, failure to thrive, seizures, coma, cerebral edema, and possibly death.


Age of onset for individuals with non-classical forms of MSUD is variable, with some presenting with symptoms as early as 2 years of age. Symptoms include poor growth and feeding, irritability, and developmental delays. These patients can also experience severe metabolic intoxication and encephalopathy during periods of sufficient catabolic stress.


MSUD is a panethnic condition but is most prevalent in the Old Order Mennonite community in Lancaster, Pennsylvania with an incidence there of 1 in 760 live births. The incidence of MSUD is approximately 1 in 185,000 live births in the general population.


A comprehensive gene panel is a helpful tool to establish a diagnosis for patients with suggestive clinical and biochemical features given the broad clinical spectrum and genetic heterogeneity of MSUD. The BCKDH complex consists of 4 subunits (E1a, E1b, E2, E3), and this panel includes testing of the genes that encode each subunit (BCKDHA for E1a, BCKDHB for E1b, DBT for E2, and DLD for E3). In addition, BCKDK and PPM1K are also included, both of which impact the activity of the BCKDH complex. Pathogenic variants in both alleles of any of these genes result in disease.


The recommended first-tier tests to screen for MSUD is a combination of biochemical tests including quantitative plasma amino acids (AAQP/ Amino Acids, Quantitative, Plasma) to measure BCAA levels and alloisoleucine and urine organic acids (OAU / Organic Acids Screen, Urine) to look for presence of toxic urine metabolites including 2-hydroxy-isovaleric acid and 2-oxo-isocaprioic acid.


Treatment of MSUD aims to normalize the concentration of BCAA by dietary restriction of these amino acids. Because BCAA belong to the essential amino acids, the dietary treatment requires frequent adjustment, which is accomplished by regular determination of BCAA and allo-isoleucine concentrations. Orthotopic liver transplantation has been successful and is an effective therapy for MSUD. 

Reference Values

An interpretive report will be provided.


All detected alterations are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Clinical Reference

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424.

2. Chuang DT, Shih VE, Wynn RM: Maple syrup urine disease (branched-chain ketoaciduria). In: Valle D, Antonarakis S, Ballabio A, Beaudet A, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill Education; 2019. Accessed October 28, 2020. Available at

3. Frazier DM, Allgeier C, Horner C, et al: Nutrition management guideline for maple syrup urine disease: an evidence- and consensus-based approach. Mol Genet Metab. 2014 Jul;112(3)210-217

4. Strauss KA, Puffenberger EG, Morton DH: Maple Syrup Urine Disease. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2006. Updated April 23, 2020. . Accessed October 28, 2020. Available at

5. Diaz VM, Camarena C, de la Vega A, et al: Liver transplantation for classical maple syrup urine disease: long-term follow-up. J Pediatr Gastroenterol Nutr. 2014 Nov;59(5):636-639

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information


81406 x3


LOINC Code Information

Test ID Test Order Name Order LOINC Value
MSUDP MSUD Gene Panel In Process


Result ID Test Result Name Result LOINC Value
608776 Test Description 62364-5
608777 Specimen 31208-2
608778 Source 31208-2
608779 Result Summary 50397-9
608780 Result 82939-0
608781 Interpretation 69047-9
608782 Resources 99622-3
608783 Additional Information 48767-8
608784 Method 85069-3
608785 Genes Analyzed 48018-6
608786 Disclaimer 62364-5
608787 Released By 18771-6

Day(s) Performed


Report Available

3 to 4 weeks