Pre-symptomatic; Screening

Establish or confirm diagnosis

Neonatal newborn screening for hereditary conditions identifiable by amino acid and acylcarnitine analysis using tandem mass spectrometry (MS/MS). 2,4 Dienoyl-CoA reductase deficiency 2-Methyl-3-hydroxybutyric aciduria 2-Methylbutyrylglycinuria 3-Hydroxy-3-methyglutaric aciduria 3-Methylcrotonyl-CoA carboxylase deficiency 3-Methylglutaconic aciduria Argininemia Argininosuccinic aciduria Benign hyperphenylalaninemia Beta-ketothiolase deficiency Biopterin defect in cofactor biosynthesis Biopterin defect in cofactor regeneration Carnitine … Neonatal newborn screening for hereditary conditions identifiable by amino acid and acylcarnitine analysis using tandem mass spectrometry (MS/MS). 2,4 Dienoyl-CoA reductase deficiency 2-Methyl-3-hydroxybutyric aciduria 2-Methylbutyrylglycinuria 3-Hydroxy-3-methyglutaric aciduria 3-Methylcrotonyl-CoA carboxylase deficiency 3-Methylglutaconic aciduria Argininemia Argininosuccinic aciduria Benign hyperphenylalaninemia Beta-ketothiolase deficiency Biopterin defect in cofactor biosynthesis Biopterin defect in cofactor regeneration Carnitine acylcarnitine translocase deficiency Carnitine palmitoyltransferase type I deficiency Carnitine palmitoyltransferase type II deficiency Carnitine transport defect Carnitine uptake defect Citrullinemia type I Citrullinemia type II Classic phenylketonuria Cobalamin disorders Glutaric acidemia type I Glutaric acidemia type II Guanidinoacetate methyltransferase deficiency Holocarboxylase synthase deficiency Homocystinuria Hypermethioninemia Isobutyrylglycinuria Isovaleric acidemia Malonic acidemia Maple syrup urine disease Medium and short-chain L-3-hydroxyacl-CoA dehydrogenase deficiency Medium-chain acyl-CoA dehydrogenase deficiency Medium-chain ketoacyl-CoA thiolase deficiency Methylmalonic acidemia with homocystinuria Methylmalonyl-CoA mutase Propionic acidemia Short chain acyl-CoA dehydrogenase deficiency Trifunctional protein deficiency Tyrosinemia type I Tyrosinemia type II Tyrosinemia type III Very long-chain acyl-CoA dehydrogenase deficiency View more

In the United States, every newborn undergoes state-mandated screening on the second day of life or before leaving the hospital. Blood from a heel prick is dripped onto a filter paper card. The blood is left to dry before sending the filter paper card along with pertinent demographic information to … In the United States, every newborn undergoes state-mandated screening on the second day of life or before leaving the hospital. Blood from a heel prick is dripped onto a filter paper card. The blood is left to dry before sending the filter paper card along with pertinent demographic information to the screening laboratory. Blood for the supplemental newborn screening is collected in the same way and then sent to the Biochemical Genetics Laboratory, after obtaining parental consent. A 1/8-inch (3-mm) disk is punched out of the blood spot onto 96-well plate. Then, the amino acids and acylcarnitines are extracted by the addition of methanol and known concentrations of isotopically labeled amino acids and acylcarnitines as internal standards. The extract is moved to another 96-well plate, dried under a stream of nitrogen, and derivatized by the addition of n-butanol hydrochloric acid. In a parallel process, succinylacetone is extracted from the residual blood spot, derivatized with an acidic hydrazine solution, evaporated and combined with the amino acid and acylcarnitine extract amino acids and acylcarnitines are measured as their butyl esters with the hydrazone derivative of succinylacetone by electrospray tandem mass spectrometry (MS/MS). The concentrations of the analytes are established by computerized comparison of ion intensities of these analytes to that of the respective internal standards.(Turgeon C, Magera MJ, Allard P, et al: Combined newborns screening for succinylacetone, amino acids, and acylcarnitines in dried blood spots. Clin Chem. 2008 Apr;54[4]:657-664; Gavrilov DK, Piazza AL, Pino G, et al: The combined impact of CLIR post-analytical tools and second tier testing on the performance of newborn screening for disorders of propionate, methionine, and cobalamin metabolism. Int J Neonatal Screen. 2020 Apr 10;6[2]:33) View more

Tests performed
Entire test performed in-house

Accuracy was assessed by method comparison of positive and negative samples and was acceptable. Intra assay precision was performed at 4 levels: CV results ranged from 1.8%-59.4% where higher CVs were obtained for physiologically low analyte concentrations near zero (N=20 each). Inter assay precision was performed at 4 levels: CV … Accuracy was assessed by method comparison of positive and negative samples and was acceptable. Intra assay precision was performed at 4 levels: CV results ranged from 1.8%-59.4% where higher CVs were obtained for physiologically low analyte concentrations near zero (N=20 each). Inter assay precision was performed at 4 levels: CV results ranged from 5.1%-71.4% where higher CVs were obtained for physiologically low analyte concentrations near zero (N=20 each). View more

Testing is only appropriate for patients less than one week of age as part of prospective newborn screening. This test is supplemental and not intended to replace state mandated newborn screening. Test is not appropriate for metabolic screening of symptomatic patients. In a few instances, falsely abnormal results may occur … Testing is only appropriate for patients less than one week of age as part of prospective newborn screening. This test is supplemental and not intended to replace state mandated newborn screening. Test is not appropriate for metabolic screening of symptomatic patients. In a few instances, falsely abnormal results may occur in the analysis of amino acid and acylcarnitine profiles. To keep the number of false-positive and false-negative results to a minimum, results are interpreted based on the metabolite profiles, the information provided on the newborn screening card, and second-tier tests for several nonspecific analytes. In 2013, testing of 71,207 newborns lead to the referral of 55 cases, 38 of them were later confirmed as true positives. These data correspond to a false-positive rate of 0.024% and a positive predictive value of 69%. Newborns discharged before 12 hours of life will need to be retested during the first week of life, eg, at the first well-child examination, as is customary for state-mandated newborn screening programs. This is necessary to avoid false-negative amino acid results due to limited protein intake on the first day of life. Carrier status (heterozygosity) for inborn errors of metabolism cannot be reliably detected by amino acid and acylcarnitine profiling. View more

Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Formal PT program

PT Provider: Help
Centers for Disease Control and Prevention Newborn Screening Quality Assurance Program, CDC DLS

Description of PT method: Help
Formal PT program

Description of internal test validation method: Help
This test was laboratory developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements.