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Bloodspot acylcarnitine and amino acid analysis in cord blood samples: efficacy and reference data from a large cohort study

  • J. H. Walter
  • A. Patterson
  • J. Till
  • G. T. N. Besley
  • G. Fleming
  • M. J. Henderson
Original Article

Summary

Background:

In order to test the feasibility of cord blood screening for inherited metabolic disease, a two-year cohort study of births in six obstetric units from five towns in the north of England was undertaken. These towns have a high prevalence of consanguineous marriages, largely among the immigrant Asian community. The purpose of the study was to determine whether early detection of metabolic disease was possible and whether early intervention would improve prognosis.

Methods:

Following parental consent, cord blood samples were collected at birth and analysed for acylcarnitine and amino acid profiles by tandem mass spectrometry in one of two laboratories. One laboratory used butylated derivatives, the other used underivatized samples. The same laboratories performed routine blood spot neonatal screening at 5–7 days of age on these babies. Patients with positive results were investigated and treated by a metabolic paediatrician as soon as possible.

Results:

24 983 births were examined. 12 952 samples were analysed as butyl derivatives, 12 031 samples were analysed underivatized. The following disorders were detected: medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (1 case), 3-methylcrotonyl-CoA carboxylase (MCC) deficiency (2 cases), maternal carnitine transporter defect (2 cases), maternal MCC (1 case). The following disorders were diagnosed subsequently but were not detected by the cord blood screening: phenylketonuria (PKU) (1 case), maple syrup urine disease (MSUD) (2 cases), argininosuccinic aciduria (1 case), methylmalonic acidaemia (MMA) (1 case), glutaric aciduria type 2 (1 case), MCAD deficiency (2 cases), 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (1 case). Comprehensive reference data for all analytes by both methods were obtained.

Conclusions:

Cord blood testing is of limited value in detecting inherited metabolic disease. The metabolites associated with most disorders examined were not elevated in cord blood. Some maternal disorders, carnitine transporter defect and 3-methlycrotonyl-CoA carboxylase deficiency, are detected. These remain of uncertain clinical significance. Comprehensive reference data have been obtained that will facilitate future interpretation of studies in cord blood.

Keywords

Cord Blood Newborn Screening Congenital Hypothyroidism Maple Syrup Urine Disease Cord Blood Sample 
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.

Abbreviations

MCAD

medium-chain acyl-CoA dehydrogenase

MCC

3-methylcrotonyl-CoA carboxylase

MMA

methylmalonic acidaemia

MSUD

maple syrup urine disease

PKU

phenylketonuria

LCHAD

long-chain hydroxyacyl-CoA dehydrogenase

VLCAD

very long-chain acyl-CoA dehydrogenase

PA

propionic acidaemia

Notes

Acknowledgements

This study was funded by a grant from the Health Foundation, UK. We acknowledge the help given to this study from all the midwives involved and from Mr Dennis Parke.

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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • J. H. Walter
    • 1
  • A. Patterson
    • 2
  • J. Till
    • 1
  • G. T. N. Besley
    • 1
  • G. Fleming
    • 1
  • M. J. Henderson
    • 2
  1. 1.Willink Biochemical Genetics UnitRoyal Manchester Children’s HospitalManchesterUK
  2. 2.Department of Chemical PathologySt James’ HospitalLeedsUK

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