Distinction Between Supplemental Newborn Screening and Acylcarnitines

Tandem MS (MS/MS or tandem mass spectrometry) is a technology that is used in various ways to measure many different compounds. Specific tandem MS methods can detect elevated levels of biochemical compounds in blood that are useful for diagnosing many inherited disorders of metabolism. It is important to realize that the different types of tandem MS tests are designed to detect specific disorders and therefore may not diagnose some diseases. Supplemental Newborn Screening is typically done in conjunction with state newborn screening and may include other tests in addition to tandem MS.To determine what your child may be tested for, one should request an information sheet from your testing laboratory. This should list what disorders will be tested for, such as amino acid disorders, organic acid disorders, fatty acid oxidation disorders or other types of disorders.

For patients with clinical symptoms or family histories of inherited metabolic disorders, diagnostic tests for specific disorders are much more appropriate than a general screen. The specific tests, such as urine organic acids, plasma amino acids, plasma or dried blood spot acylcarnitines should be determined and ordered by clinicians based on the clinical symptoms.

Supplemental Newborn Screening by tandem MS: In our laboratory, the Supplemental Newborn Screening is done by tandem MS for amino acids and acylcarnitines. The test can detect more than 30 inherited disorders of amino acid, organic acid and fatty acid metabolism. It is an inexpensive screening test with dried blood spots designed for screening healthy newborns at 2-3 days of age. It is not recommended for the diagnosis of children with clinical symptoms. Cut offs for normal levels of amino acids and acylcarnitines in newborns are chosen to minimize false positives. Approximately 1% shows some slight elevation of an amino acid or acylcarnitine which causes us to request a repeat dried blood spot card to see if the slight elevation is significant. Usually the repeat is normal. The false negative rate is not known but is believed to be very low. In order for this test to be inexpensive ($25), it is highly automated. The quantitative results are analyzed automatically by tandem MS computer programs for “normality” using cut offs established for different groups of subjects. Although the screening is most accurate for newborns it is still worthwhile to perform for older infants if they were not screened in the newborn period.

Quantitative Acylcarnitine profile by tandem MS is a more expensive test designed for the differential diagnosis of fatty acid oxidation and organic acid disorders in children with clinical symptoms or family histories suggestive of these disorders. This can be performed on dried blood spots, plasma, postmortem blood (or amniotic fluid with prior consultation). Because it is intended for diagnostic evaluation, the cut offs used for acylcarnitines are lower and every profile is examined by a technician for any abnormalities in the mass spectrum, including peaks that are not part of the quantitative analysis. Every profile is reviewed by an experienced professional and reported with a professional interpretation. The acylcarnitine profile does not include amino acid disorders.

Dr. Larry Sweetman, PhD and Staff

Institute of Metabolic Disease

Baylor University Medical Center