Screening

Establish or confirm diagnosis

First-tier newborn screen for the lysosomal disorders: Fabry, Gaucher, Krabbe, mucopolysaccharidosis I (MPS-I), Niemann-Pick types A and B, and Pompe (glycogen storage disorder type II). First-tier newborn screen for the peroxisomal disorder: X-linked adrenoleukodystrophy; may also detect Zellweger spectrum disorders. This test is supplemental and not intended to replace state-mandated … First-tier newborn screen for the lysosomal disorders: Fabry, Gaucher, Krabbe, mucopolysaccharidosis I (MPS-I), Niemann-Pick types A and B, and Pompe (glycogen storage disorder type II). First-tier newborn screen for the peroxisomal disorder: X-linked adrenoleukodystrophy; may also detect Zellweger spectrum disorders. This test is supplemental and not intended to replace state-mandated newborn screening. Test is not intended for metabolic screening of symptomatic patients. View more

Two 1/8-inch dried blood spots (DBS) are excised from a single specimen. The enzymes are extracted by incubating the specimens with a mix of substrate and internal standard for acid sphingomyelinase (ASM), beta-glucocerebrosidase (ABG), alpha-glucosidase (GAA), alpha-galactosidase (GLA), galactocerebrosidase (GALC) and alpha-L-iduronidase (IDUA). The sample is then purified by liquid-liquid … Two 1/8-inch dried blood spots (DBS) are excised from a single specimen. The enzymes are extracted by incubating the specimens with a mix of substrate and internal standard for acid sphingomyelinase (ASM), beta-glucocerebrosidase (ABG), alpha-glucosidase (GAA), alpha-galactosidase (GLA), galactocerebrosidase (GALC) and alpha-L-iduronidase (IDUA). The sample is then purified by liquid-liquid extraction. The second DBS is extracted with methanol containing d4-C26 lysophosphatidylcholines (LPC). The resulting extracts are then combined, evaporated, and reconstituted before analysis by tandem mass spectrometry.(Tortorelli S, Turgeon C, Gavrilov D, et al: Simultaneous testing for 6 lysosomal storage disorders and X-adrenoleukodystrophy in dried blood spots by tandem mass spectrometry. Clin Chem. 2016;62[9]:1248-1254) View more

Tests performed
Entire test performed in-house

Accuracy was assessed by analysis of positive and negative specimens; all samples were clinically concordant. Intra assay precision was performed at 7 levels: CV results ranged from 3%-244% where higher CVs were obtained for physiologically low analyte concentrations near zero (N=20 each). Inter assay precision was performed at 3 levels: … Accuracy was assessed by analysis of positive and negative specimens; all samples were clinically concordant. Intra assay precision was performed at 7 levels: CV results ranged from 3%-244% where higher CVs were obtained for physiologically low analyte concentrations near zero (N=20 each). Inter assay precision was performed at 3 levels: CV results ranged from 7%-29% where higher CVs were obtained for physiologically low analyte concentrations near zero (N=20 each). View more

Carrier status (heterozygosity) for these conditions cannot be reliably detected. A positive test result is strongly suggestive of a diagnosis but requires follow-up by stand-alone biochemical or molecular assay, which is best coordinated by local genetics providers. Some cases with milder or later onset disease may not display sufficiently abnormal … Carrier status (heterozygosity) for these conditions cannot be reliably detected. A positive test result is strongly suggestive of a diagnosis but requires follow-up by stand-alone biochemical or molecular assay, which is best coordinated by local genetics providers. Some cases with milder or later onset disease may not display sufficiently abnormal results during the newborn period and, therefore, yield false-negative results. View more

Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Formal PT program & Inter-Laboratory

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

Description of PT method: Help
Formal PT program and Inter-laboratory comparison with outside laboratory(s)

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.