Screening

Establish or confirm diagnosis

First-tier newborn screen for the lysosomal disorders: Fabry, Gaucher, Krabbe, mucopolysaccharidosis I (MPS-I), mucopolysaccharidosis II (MPS-II), 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 … First-tier newborn screen for the lysosomal disorders: Fabry, Gaucher, Krabbe, mucopolysaccharidosis I (MPS-I), mucopolysaccharidosis II (MPS-II), 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 a method comparison of positive and negative specimens (N=75); all samples were clinically concordant with the following exceptions: One Fabry Carrier sample was not clinically concordant with the reference assay. The GLA result for the reference assay was above the cutoff and considered normal, while the … Accuracy was assessed by a method comparison of positive and negative specimens (N=75); all samples were clinically concordant with the following exceptions: One Fabry Carrier sample was not clinically concordant with the reference assay. The GLA result for the reference assay was above the cutoff and considered normal, while the new assay GLA value was below the cutoff and considered abnormal. Because female carriers of pathogenic GLA variants do not have consistently reduced GLA activity, this can be considered acceptable. Two normal samples were not clinically concordant with the reference assay for LPCs. The result for C26-LPC for the reference assay was above the cutoff, while the new assay had the value below the cutoff as expected for samples from unaffected individuals. Intra assay precision was performed at 2 levels quantitatively and one near zero (deficient) level for enzymes (N=20): CV results ranged from 4.8%-24.9%. The enzyme deficient samples were all clinically concordant. Inter assay precision was performed at 2 levels quantitatively and one near zero (deficient) level for enzymes (N=20): CV results ranged from 8.9%-23.0%. The enzyme deficient samples were all clinically concordant. 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.