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

Summary

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.

Abbreviations

C0

free carnitine

C2

acetylcarnitine

C3

propionylcarnitine

C4

isobutyryl/butyrylcarnitine

C5OH

hydroxyisovalerylcarnitine

C6

hexanoylcarnitine

C8

octanoylcarnitine

C10:1

decenoylcarnitine

CblC

cobalamin C

CDC

Centers for Disease Control and Prevention

DBS

dried blood spot

DHPR

dihydropteridine reductase

HPA

hyperphenylalaninaemia

IBD

isobutyryl-CoA dehydrogenase

LC-MS/MS

liquid chromatography–tandem mass spectrometry

MCAD

medium-chain acyl-CoA dehydrogenase

MMA

methylmalonic aciduria

MS/MS

tandem mass spectrometry

NARP

neuropathy ataxia and retinis pigmentosa

PKU

phenylketonuria

SCAD

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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