Follow-up of patients with maple syrup urine disease
Monitoring of dietary compliance for patients with maple syrup urine disease
This test is appropriate for follow-up and dietary monitoring of patients with maple syrup urine disease.
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
Portions of this test are covered by patents held by Quest Diagnostics
Allo-Isoleucine
Isoleucine
Leucine
Maple Syrup Urine Disease (MSUD)
MSUD (Maple Syrup Urine Disease)
Valine
Maple Syrup Disease
Branched-chain ketoacid dehydrogenase (BCKDH)
Plasma
1. Patient's age is required.
2. Include family history, clinical condition (asymptomatic or acute episode), diet, and drug therapy information.
Patient Preparation: Fasting (overnight preferred, 4 hours minimum). Infants should be drawn just before next feeding (2-3 hours without total parenteral nutrition: TPN if possible).
Collection Container/Tube:
Preferred: Green top (sodium heparin)
Acceptable: Lavender top (EDTA), plasma gel tube, or green top (lithium heparin)
Submission Container/Tube: Plastic vial
Specimen Volume: 0.5 mL
Collection Instructions:
1. Collect specimen and place on wet ice. Note: Thrombin-activated tubes should not be used for collection.
2. Centrifuge immediately or within 4 hours of collection if specimen is kept at refrigerated temperature.
3. Being careful to ensure that no buffy coat is transferred, aliquot plasma into a plastic vial and freeze.
If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
0.3 mL
Gross hemolysis | OK |
Gross lipemia | OK |
Gross icterus | OK |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Plasma | Frozen | 14 days |
Follow-up of patients with maple syrup urine disease
Monitoring of dietary compliance for patients with maple syrup urine disease
Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by the deficiency of the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex. The BCKDH complex is involved in the metabolism of the branched-chain amino acids (BCAA): isoleucine, leucine, and valine. 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 thiamin administration. Classic MSUD, the most common and most severe form, presents in the neonate with feeding intolerance, failure to thrive, vomiting, lethargy, and maple syrup odor to urine and cerumen. If untreated, it progresses to irreversible intellectual diabilities, hyperactivity, failure to thrive, seizures, coma, cerebral edema, and possibly death.
Age of onset for individuals with variant forms of MSUD is variable and some have initial 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 of 1:760 live births. The incidence of MSUD is approximately 1:185,000 live births in the general population.
Treatment of MSUD aims to normalize the concentration of BCAA by dietary restriction of these amino acids. Because BCAA are 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 used with success and is an effective therapy for MSUD.
ISOLEUCINE
< or =23 months: 31-105 nmol/mL
2-17 years: 30-111 nmol/mL
> or =18 years: 36-107 nmol/mL
LEUCINE
< or =23 months: 48-175 nmol/mL
2-17 years: 51-196 nmol/mL
> or =18 years: 68-183 nmol/mL
VALINE
< or =23 months: 83-300 nmol/mL
2-17 years: 106-320 nmol/mL
> or =18 years: 136-309 nmol/mL
ALLO-ISOLEUCINE
< or =23 months: <2 nmol/mL
2-17 years: <3 nmol/mL
> or =18 years: <5 nmol/mL
The quantitative results of isoleucine, leucine, valine, and allo-isoleucine with age-dependent reference values are reported without added interpretation. When applicable, reports of abnormal results may contain an interpretation based on available clinical interpretation.
Reference values are for fasting patients.
1. Chuang DT, Shih VE, Max Wynn RR. Maple syrup urine disease (Branched-chain ketoaciduria). In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw Hill; 2019. Accessed October 5, 2022. https://ommbid.mhmedical.com/content.aspx?bookid=2709§ionid=225084607
2. 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. doi: 10.1016/j.ymgme.2014.05.006
3. Strauss KA, Puffenberger EG, Morton DH: Maple syrup urine disease. In: RA Pagon, MP Adam, HH Ardinger, et al, eds. GeneReviews[Internet]. University of Washington, Seattle; 2006. Updated April 23, 2020. Accessed October 5, 2022. Available at www.ncbi.nlm.nih.gov/books/NBK1319
4. 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. doi: 10.1097/MPG.0000000000000469
5. Blackburn PR, Gass JM, Vairo FPE, et al:. Maple syrup urine disease: mechanisms and management. Appl Clin Genet. 2017 Sep 6;10:57-66. doi: 10.2147/TACG.S125962
Quantitative analysis of amino acids is performed by liquid chromatography tandem mass spectrometry (LC-MS/MS) by labeling amino acids present in plasma, urine, and spinal fluid with aTRAQ Reagent 121. Samples are dried and reconstituted with aTRAQ Reagent 113-labeled Standard Mix. Amino acids are separated and detected by LC-MS/MS. The concentrations of amino acids are established by comparison of their ion intensity (121-labeled amino acids) to that of their respective internal standards (113-labeled amino acids).(Unpublished Mayo method)
Monday through Friday
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.
82136
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
AAMSD | Amino Acid, MSUD Panel, P | 94566-7 |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
32446 | Valine | 94567-5 |
32447 | Isoleucine | 94568-3 |
32448 | Leucine | 94569-1 |
32449 | Allo-isoleucine | 94570-9 |
32450 | Interpretation (AAMSD) | 49247-0 |