Allo-isoleucine, Blood Spot
Evaluation of newborn screening specimens that test positive for branched-chain amino acids elevations
Follow-up of patients with maple-syrup urine disease
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Second-tier test for abnormal newborn screen and follow-up of patients with maple syrup urine disease.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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). Classic MSUD 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 mental retardation, hyperactivity, failure to thrive, seizures, coma, cerebral edema, and possibly death.
MSUD is a pan-ethnic condition, but is most prevalent in the Old Order Mennonite community in Lancaster, Pennsylvania with an incidence there of 1:760 live births. The incidence of MSUD is approximately 1:200,000 live births in the general population.
Newborn screening includes the measurement of BCAA (Leu, Ile, and Val), which are elevated in MSUD. However, unaffected infants receiving total parenteral nutrition frequently have increased levels of BCAA, a situation that often triggers unnecessary follow-up investigations. Abnormal concentrations of allo-isoleucine (Allo-Ile) are pathognomonic for MSUD. The determination of Allo-Ile (second-tier testing) in the same newborn screening specimens that reveals elevated BCAA allows for positive identification of patients with MSUD and differentiation from BCAA elevations due to dietary artifacts, reducing the occurrence of false-positive newborn screening results.
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-Ile concentrations.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Allo-isoleucine: <2 nmol/mL
Leucine: 35-215 nmol/mL
Isoleucine: 13-130 nmol/mL
Valine: 51-325 nmol/mL
An interpretive report will also be provided.
Allo-isoleucine is nearly undetectable in individuals not affected by maple-syrup urine disease (MSUD). Accordingly, its presence is diagnostic for MSUD, and its absence is sufficient to rule out MSUD.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
No significant cautionary statements.
In a blinded study containing specimens obtained from maple-syrup urine disease (MSUD) cases (n=16), non-MSUD patients treated with total parenteral nutrition (n=19), and healthy controls (n=541), this assay correctly identified all MSUD and non-MSUD cases.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Chace DH, Hillman SL, Millington DS, et al: Rapid diagnosis of maple syrup urine disease in blood spots from newborns by tandem mass spectrometry. Clin Chem 1995;41:62-68
2. Simon E, Fingerhut R, Baumkotter J, et al: Maple syrup urine disease: Favorable effect of early diagnosis by newborn screening on the neonatal course of the disease. J Inherit Metab Dis 2006;29:532-537
3. Morton DH, Strauss KA, Robinson DL, et al: Diagnosis and treatment of maple syrup disease: a study of 36 patients. Pediatrics 2002;109:999-1008
4. Strauss KA, Puffenberger EG, Morton DH: Maple syrup urine disease. In GeneReviews Edited by RA Pagon, MP Adam, HH Ardinger, et al: University of Washington, Seattle; 1993-2015. 2006 Jan 30 (Updated 2013 May 9). Accessed August 2015. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1319/