Allo-isoleucine, Blood Spot

CPT CODE:

USEFUL FOR:

Evaluation of newborn screening samples that test positive for BCAA elevations
Follow-up of patients with MSUD

SPECIMEN REQUIRED:

2 blood spots from local newborn screening card (at least 1 spotshould be complete, unpunched). If collection of a new specimenis necessary, let blood dry on the "Newborn Screening Card"(Supply T493) at ambient temperature in a horizontal position for3 hours.  An alternative blood collection option for patients >1 year of age is fingerstick. Please include type of feeding information on thecollection card.Note:    1. Do not expose specimen to heat or direct sunlight.                  2. Do not stack wet specimens.                  3. Do not use devices or capillary tubes containing EDTA                       to collect specimen.                  4. Keep specimen dry.

TRANSPORT TEMPERATURE:

Ambient\Refrig NO\Frozen NO

CLINICAL INFORMATION:

Maple-syrup urine disease (MSUD) is an autosomal recessive 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 panethnic condition, but is most prevalent in the Old Order Mennonite community in Lancaster, Pennsylvania. The incidence of MSUD is approximately 1:200,000 live births in the general population and 1:760 live births among the Old Order Mennonites.
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 artefacts, 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.

CLINICAL INTERPRETATION:

Allo-Ile is nearly undetectable in individuals not affected by MSUD.Accordingly, its presence is diagnostic for MSUD, and its absence is sufficient to rule-out MSUD.

REFERENCE VALUES:

Allo-isoleucine   <2 umol/L

Leucine                35-215 umol/L

Isoleucine            13-130 umol/L

Valine                   51-325 umol/L

An interpretive report will also be provided.