Outcome of Expanded Newborn Screening by Means of MS/MS in 250 000 Newborns

Confirmed CasesBefore Result of ScreeningAge at Start of Treatment (D)Current Clinical StatusObservation Period (Mo)
SymptomaticDiagnosis made priorAsymptomaticSymptomaticDied
Amino acidemias
 PKU24Not investigated*
 non-PKU-hyperphenylalaninemia31Not investigated*
 Tyrosinemia I1+65+5
 Maple syrup urine disease1++10(+)38
 MSUD-variant form18+24
 Citrullinemia-variant forms50/50/5–/–/–/–/125/514/6/9/3/6
 Nonketotic hyperglycinemia1++2+4 days
FAO disorders
 Long-chain 3-OH acyl-CoA dehydrogenase/ mitochondrial trifunctional protein1+++1 d
 Very long-chain acyl-CoA dehydrogenase-variant form1185+35
 MCAD128.5 (7–90)*12/1217.0 (1–38)
 MCAD-variant forms465/39/18/124/416/27/21/19
 Short-chain acyl-CoA dehydrogenase-variant forms3−/−/−3/39/25/14
 Multiple acyl-CoA dehydrogenase1+6+3.5
 Carnitine transporter defect160+15
 Carnitine palmitoyltransferase II128+22
Organic acidurias
 Propionic aciduria1++4(+)14
 Methylmalonic aciduria-variant form1+12
 Cobalamin C/D deficiency2+/++/−28/6+/+30/7
 Glutaric aciduria type I318/210/12+(+)/(+)12/32/11
 Isovaleric aciduria410/7/11/114/431/19/14/12
 3-Methylcrotonyl-CoA carboxylase27/72/225/7
 3-Methylcrotonyl-CoA carboxylase-variant forms44/412/12/13/4
Amino acidemias-total654/653/659.0 (2–65)§8/101/101/107.5 (0.1–38)§
FAO disorders-total242/241/2411.0 (6–185)§22/240/242/2419.0 (1–38)§
Organic acidurias-total173/172/1710.5 (2–210)§12/175/170/1712.0 (4–32)§
MS/MS screening-total1069/1066/10610.0 (2–210)§42/516/513/5113.5 (0.1–38)§
  • MSUD indicates maple syrup urine disease.

  • * Not investigated in this study. A similar, overlapping cohort was recently evaluated by our group.26

  • Four of these children were not treated; in the remaining 1, treatment was started at age 12 days.

  • § Median (range).

  • The PKU and non-PKU-HPA groups were excluded but should be considered asymptomatic.