Four years of expanded newborn screening in Portugal with tandem mass spectrometry.
BACKGROUND
The Portuguese Neonatal Screening Programme (PNSP) was started in 1979 for phenylketonuria (2,590,700 newborns screened; prevalence 1:11,031) and, shortly after, for congenital hypothyroidism (2,558,455 newborns screened; prevalence 1:3,174). In 2004, expanded neonatal screening was implemented in the National Laboratory. The programme is not mandatory and has 99.8% coverage of the country (including Madeira and the Azores islands).


METHODS
In the past 4 years, 316,243 neonates were screened with the use of tandem mass spectrometry (MS/MS) to test for selected amino acids and acylcarnitines.


RESULTS
During this time, 132 patients were identified with 24 different inherited metabolic diseases (classic forms and variants). To date, the global frequency for all disorders integrated into the PNSP is estimated to be 1:1,380, with 1:2,396 for metabolic disorders. A total of 379 tests (0.12%) were classified as having false positive results, yielding an overall specificity of 99.9%. Despite the low frequency of several disorders, the positive predictive value of the overall MS/MS screening was found to be 26%, reflecting high diagnostic specificity of the method. Diagnostic sensitivity of extended screening for the different groups of disorders was 100%. Eight cases of maternal disorders [three glutaric aciduria type I, one carnitine transporter defect, and four 3-methylcrotonyl coenzyme A (CoA) carboxylase deficiency] were also detected through newborn screening.


CONCLUSIONS
Our data support the advantage of a centralised laboratory for screening an elevated number of samples and making decisions if relying on a clinical network able to provide fast treatment and a good outcome in the screened cases.
Vilarinho
Laura
L
Newborn Screening Unit, Medical Genetics Center, National Institute of Health, INSA, Praca Pedro Nunes 88, 4099-028 Porto, Portugal, laura.vilarinho@igm.min-saude.pt
Rocha
Hugo
H
Sousa
Carmen
C
Marcão
Ana
A
Fonseca
Helena
H
Bogas
Mário
M
Osório
Rui Vaz
RV
D000596:Amino Acids / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D002331:Carnitine / Q000031:analogs & derivatives / Q000032:analysis; D042241:Early Diagnosis; D005189:False Positive Reactions; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D015997:Neonatal Screening / Q000379:methods*; D010641:Phenotype; D011174:Portugal / Q000453:epidemiology; D011237:Predictive Value of Tests; D015995:Prevalence; D011379:Prognosis; D015397:Program Evaluation; D053719:Tandem Mass Spectrometry; D013997:Time Factors
D000596:Amino Acids; D015415:Biomarkers; C116917:acylcarnitine; D002331:Carnitine