Newborn screening for methylmalonic acidurias--optimization by statistical parameter combination.
With the introduction of tandem mass spectrometry, newborn screening for disorders of propionate metabolism became widely available. However, there is controversy whether population screening for these disorders should be performed. The most widely used primary metabolite C(3) itself has a poor specificity or lacks 100% sensitivity for milder forms and/or defects of cobalamin metabolism. Strategies to improve specificity have included the calculation of metabolite ratios (e.g. C(3)/C(2)) or second-tier strategies with analysis of methylmalonic acid or 2-methylcitric acid from the primary screening specimen. We report the results of a new statistical approach to identify parameter combinations that allow for 100% sensitivity as well as increased specificity. The promising results of this alternative approach will have to be substantiated on larger data sets.
Sektion für angeborene Stoffwechselkrankheiten, Zentrum für Kinder- und Jugendmedizin, INF 153, D-69120, Heidelberg, Germany. martin.lindner@med.uni-heidelberg.de
M
M
Lindner
S
S
Ho
S
S
Kölker
G
G
Abdoh
G F
GF
Hoffmann
P
P
Burgard
D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis*; D006801:Humans; D007231:Infant, Newborn; D008764:Methylmalonic Acid / Q000652:urine*; D015997:Neonatal Screening; D011422:Propionates / Q000378:metabolism*; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry
D011422:Propionates; D008764:Methylmalonic Acid; C029658:propionic acid