Journal of Inherited Metabolic Disease

, Volume 31, Supplement 2, pp 395–404 | Cite as

Progress in expanded newborn screening for metabolic conditions by LC-MS/MS in Tuscany: Update on methods to reduce false tests

  • G. la Marca
  • S. Malvagia
  • B. Casetta
  • E. Pasquini
  • M. A. Donati
  • E. Zammarchi
Short Report


We report on our 6-year experience of expanded newborn screening by tandem mass spectrometry in Tuscany (Italy), the first Italian Region to screen all newborns for more than 40 inborn errors of metabolism: organization, diseases observed and updates on methods to reduce false-positive and false-negative tests are described. Blood collection is recommended between 48 and 72  h of life. Blood spots are sent daily by courier to laboratory. When a positive result occurs, two subsequent procedures are followed: for disorders with possible acute metabolic decompensation, the baby is immediately recalled and clinical examinations and confirmatory tests are performed; for the other disorders, the nursery provides for a second blood spot. If the test is positive, clinical examinations and confirmatory tests are performed. In both cases, if confirmatory tests are positive, a treatment and a follow-up programme are started. Up to now, spots from 160 000 infants have been analysed and 80 affected patients have been identified (disorders of amino acids, organic acids and fatty acids metabolism). We describe adjustments to cut-off values, the introduction of a second-tier test for propionic acidaemia and for methylmalonic aciduria, the inclusion of succinylacetone in the panel of metabolites, and protocols for premature infants and for newborns on parenteral nutrition or transfused. These changes resulted in a reduction in recalls from 1.37% to 0.32% and consequently of working time and parental stress. Avoiding false-negatives by using more specific markers and minimizing the false-positive rate with second-tier testing is important for a successful newborn screening programme.


Newborn Screening Methylmalonic Neonatal Screening Methylmalonic Acid Newborn Screening Programme 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



free carnitine
















cobalamin C


Centers for Disease Control and Prevention


dried blood spot


dihydropteridine reductase




isobutyryl-CoA dehydrogenase


liquid chromatography–tandem mass spectrometry


medium-chain acyl-CoA dehydrogenase


methylmalonic aciduria


tandem mass spectrometry


neuropathy ataxia and retinis pigmentosa




short-chain acyl-CoA dehydrogenase


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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • G. la Marca
    • 1
    • 4
    • 5
  • S. Malvagia
    • 1
  • B. Casetta
    • 2
  • E. Pasquini
    • 1
  • M. A. Donati
    • 1
  • E. Zammarchi
    • 3
  1. 1.Meyer Children’s Hospital, Metabolic UnitFlorenceItaly
  2. 2.Applied BiosystemsMonzaItaly
  3. 3.Department of PaediatricsUniversity of FlorenceFlorenceItaly
  4. 4.Clinical and Preclinical Pharmacology DepartmentUniversity of FlorenceFlorenceItaly
  5. 5.Meyer Children’s HospitalFlorenceItaly

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