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



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.


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.


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.


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.


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.



medium-chain acyl-CoA dehydrogenase


3-methylcrotonyl-CoA carboxylase


methylmalonic acidaemia


maple syrup urine disease




long-chain hydroxyacyl-CoA dehydrogenase


very long-chain acyl-CoA dehydrogenase


propionic acidaemia



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.


  1. de Baulny HO, Benoist JF, Rigal O, Touati G, Rabier D, Saudubray JM (2005) Methylmalonic and propionic acidaemias: management and outcome. J Inherit Metab Dis 28(3): 415–423. doi: 10.1007/s10545-005-7056-1.PubMedCrossRefGoogle Scholar
  2. Dionisi-Vici C, Deodato F, Roschinger W, Rhead W, Wilcken B (2006) ‘Classical’ organic acidurias, propionic aciduria, methylmalonic aciduria and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry. J Inherit Metab Dis 29(2–3): 383–389. doi: 10.1007/s10545-006-0278-z.PubMedCrossRefGoogle Scholar
  3. Hutchesson AC, Bundey S, Preece MA, Hall SK, Green A (1998) A comparison of disease and gene frequencies of inborn errors of metabolism among different ethnic groups in the West Midlands, UK. J Med Genet 35(5): 366–370.PubMedCrossRefGoogle Scholar
  4. Leonard JV (1995) The management and outcome of propionic and methylmalonic acidaemia. J Inherit Metab Dis 18(4): 430–434. doi: 10.1007/BF00710054.PubMedCrossRefGoogle Scholar
  5. Leonard JV, Daish P, Naughten ER, Bartlett K (1984) The management and long term outcome of organic acidaemias. J Inherit Metab Dis 7(Supplement 1): 13–17.PubMedCrossRefGoogle Scholar
  6. Nassogne MC, Heron B, Touati G, Rabier D, Saudubray JM (2005) Urea cycle defects: management and outcome. J Inherit Metab Dis 28(3): 407–414. doi: 10.1007/s10545-005-0303-7.PubMedCrossRefGoogle Scholar
  7. Naughten ER, Jenkins J, Francis DE, Leonard JV (1982) Outcome of maple syrup urine disease. Arch Dis Child 57(12): 918–921.PubMedCrossRefGoogle Scholar
  8. Patterson A, Pourfarzam M, Henderson MJ (2000) The utility of cord blood analysis in the diagnosis of organic acidaemias. J Inherit Metab Dis 23(Supplement 1): 84.Google Scholar
  9. Phillips P, Dalton RN, Besley G, et al (2005) Newborn screening for MCAD deficiency at one week of age. J Inherit Metab Dis 28(Supplement 1): 9.Google Scholar
  10. Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF (2003) Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications. Pediatrics 111(6 Pt 1): 1399–1406. doi: 10.1542/peds.111.6.1399.PubMedCrossRefGoogle Scholar
  11. Shortland GJ, Besley G, Bonham J, et al (2006) Newborn screening for MCADD: findings from a multicentre UK prospective collaborative study. J Inherit Metab Dis 29(Supplement 1): 19.Google Scholar
  12. Surtees RA, Matthews EE, Leonard JV (1992) Neurologic outcome of propionic acidemia. Pediatr Neurol 8: 333–337. doi: 10.1016/0887-8994(92)90085-D.PubMedCrossRefGoogle Scholar
  13. van der Meer SB, Poggi F, Spada M, et al (1996) Clinical outcome and long-term management of 17 patients with propionic acidaemia. Eur J Pediatr 155(3): 205–210. doi: 10.1007/BF01953939.PubMedCrossRefGoogle Scholar
  14. Vijay S, Patterson A, Olpin S, et al (2006) Carnitine transporter defect: diagnosis in asymptomatic adult women following analysis of acylcarnitines in their newborn infants. J Inherit Metab Dis 29(5): 627–630. doi: 10.1007/s10545-006-0376-y.PubMedCrossRefGoogle Scholar
  15. Wilcken B, Haas M, Joy P, et al (2007) Outcome of neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency in Australia: a cohort study. Lancet 369(9555): 37–42. doi: 10.1016/S0140-6736(07)60029-4.PubMedCrossRefGoogle Scholar
  16. Wiley V, Carpenter K, Wilcken B (1999) Newborn screening with tandem mass spectrometry: 12 months’ experience in NSW Australia. Acta Paediatr Suppl 88(432): 48–51. doi: 10.1080/080352599750029376.PubMedCrossRefGoogle Scholar

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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