Expanded metabolic screening utilizing tandem mass spectrometry: The Massachusetts experience in the first year

Abstract

From February through November 1999, the first 60,000 newborns (of an annual birth cohort of 80,000) in MA were screened by tandem mass spectrometry (MS) for 20 metabolic disorders, as an expansion beyond 3 amino acids (phenylalanine, methionine, leucine) and 6 other routine screens: galactosemia, biotinidase deficiency, hypothyroidism, CAH, hemoglobinopathy and toxoplasmosis. [Screening methods for the latter 6 were unchanged.]

The MS expanded screening disease categories included:

a. Amino Acids (AA): arginine, omithine, citrulline (urea cycle defects); tyrosine (tyrosinemia type 1 and 2). No cases were identified.

b. Organic Acids (OA): propionic (PPA), methylmalonic (MMA) and glutaric acidurias (GA1 or 2), HMG Co A lyase deficiency, ketothiolase deficiency. Two PPA were identified.

c. Fatty Acid Oxidation (FOD) defects: short, medium and long chain acyl-Co A dehydrogenase deficiencies (SCAD, MCAD, LCAD, LCHAD, VLCAD) and carnitine palmitoyl transferase deficiency (CPT-2). Two SCAD, one MCAD and one CPT-2 were identified.

Of the 6 detections, 5 were asymptomatic. The infant with CPT-2 deficiency died the day the blood spot was received.

Conclusion: By MS, the 3 original AA were detected in the usual frequency. For OA, the prevalence was approximately as expected, MCAD was less than expected, and SCAD may be more common than we had inferred from rare published reports.