Skip to main content
PMC home page
Archives of Disease in Childhood. Fetal and Neonatal Edition logoLink to Archives of Disease in Childhood. Fetal and Neonatal Edition
. 2001 Sep;85(2):F105–F109. doi: 10.1136/fn.85.2.F105

Evaluation of newborn screening for medium chain acyl-CoA dehydrogenase deficiency in 275 000 babies

K Carpenter, V Wiley, K Sim, D Heath, B Wilcken
PMCID: PMC1721303  PMID: 11517203

Abstract

OBJECTIVE—To evaluate newborn screening by tandem mass spectrometry for detection of medium chain acyl-CoA dehydrogenase (MCAD) deficiency, a fatty acid oxidation disorder with significant mortality in undiagnosed patients.
DESIGN—The following were studied: (a) 13 clinically detected MCAD deficient subjects, most homozygous for the common A985G mutation, whose newborn screening sample was available; (b) 275 653 consecutive neonates undergoing routine newborn screening. Screened infants with blood octanoylcarnitine levels ⩾ 1 µmol/l were analysed for the A985G mutation, had analysis of plasma and repeat blood spot acylcarnitines and urinary organic acids, and had fibroblast fatty acid oxidation or acylcarnitine studies.
RESULT—Twelve of the 13 patients later diagnosed clinically had newborn octanoylcarnitine levels > 2.3 µmol/l. Twenty three screened babies had initial octanoylcarnitine levels ⩾ 1 µmol/l. Eleven of 12 babies with persistent abnormalities had metabolite and/or enzyme studies indicating MCAD deficiency. Only four were homozygous for the A985G mutation, the remainder carrying one copy.
CONCLUSIONS—Most patients with symptomatic MCAD deficiency could be detected by newborn screening. Infants actually detected had a lower frequency of A985G alleles than clinically diagnosed cases and may have a lower risk of becoming symptomatic.



Full Text

The Full Text of this article is available as a PDF (120.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andresen B. S., Bross P., Udvari S., Kirk J., Gray G., Kmoch S., Chamoles N., Knudsen I., Winter V., Wilcken B. The molecular basis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in compound heterozygous patients: is there correlation between genotype and phenotype? Hum Mol Genet. 1997 May;6(5):695–707. doi: 10.1093/hmg/6.5.695. [DOI] [PubMed] [Google Scholar]
  2. Blakemore A. I., Singleton H., Pollitt R. J., Engel P. C., Kolvraa S., Gregersen N., Curtis D. Frequency of the G985 MCAD mutation in the general population. Lancet. 1991 Feb 2;337(8736):298–299. doi: 10.1016/0140-6736(91)90907-7. [DOI] [PubMed] [Google Scholar]
  3. Christodoulou J., Hoare J., Hammond J., Ip W. C., Wilcken B. Neonatal onset of medium-chain acyl-coenzyme A dehydrogenase deficiency with confusing biochemical features. J Pediatr. 1995 Jan;126(1):65–68. doi: 10.1016/s0022-3476(95)70504-x. [DOI] [PubMed] [Google Scholar]
  4. Clayton P. T., Doig M., Ghafari S., Meaney C., Taylor C., Leonard J. V., Morris M., Johnson A. W. Screening for medium chain acyl-CoA dehydrogenase deficiency using electrospray ionisation tandem mass spectrometry. Arch Dis Child. 1998 Aug;79(2):109–115. doi: 10.1136/adc.79.2.109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Curtis D., Blakemore A. I., Engel P. C., Macgregor D., Besley G., Kolvraa S., Gregersen N. Heterogeneity for mutations in medium chain acyl-CoA dehydrogenase deficiency in the UK population. Clin Genet. 1991 Oct;40(4):283–286. doi: 10.1111/j.1399-0004.1991.tb03097.x. [DOI] [PubMed] [Google Scholar]
  6. Gregersen N., Blakemore A. I., Winter V., Andresen B., Kølvraa S., Bolund L., Curtis D., Engel P. C. Specific diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in dried blood spots by a polymerase chain reaction (PCR) assay detecting a point-mutation (G985) in the MCAD gene. Clin Chim Acta. 1991 Nov 9;203(1):23–34. doi: 10.1016/0009-8981(91)90153-4. [DOI] [PubMed] [Google Scholar]
  7. Heptinstall L. E., Till J., Wraith J. E., Besley G. T. Common MCAD mutation in a healthy parent of two affected siblings. J Inherit Metab Dis. 1995;18(5):638–639. doi: 10.1007/BF02436011. [DOI] [PubMed] [Google Scholar]
  8. Iafolla A. K., Thompson R. J., Jr, Roe C. R. Medium-chain acyl-coenzyme A dehydrogenase deficiency: clinical course in 120 affected children. J Pediatr. 1994 Mar;124(3):409–415. doi: 10.1016/s0022-3476(94)70363-9. [DOI] [PubMed] [Google Scholar]
  9. Matsubara Y., Narisawa K., Tada K. Medium-chain acyl-CoA dehydrogenase deficiency: molecular aspects. Eur J Pediatr. 1992 Mar;151(3):154–159. doi: 10.1007/BF01954373. [DOI] [PubMed] [Google Scholar]
  10. Naylor E. W., Chace D. H. Automated tandem mass spectrometry for mass newborn screening for disorders in fatty acid, organic acid, and amino acid metabolism. J Child Neurol. 1999 Nov;14 (Suppl 1):S4–S8. doi: 10.1177/0883073899014001021. [DOI] [PubMed] [Google Scholar]
  11. Olpin S. E., Manning N. J., Pollitt R. J., Bonham J. R., Downing M., Clark S. The use of [9,10-3H]myristate, [9,10-3H]palmitate and [9,10-3H]oleate for the detection and diagnosis of medium and long-chain fatty acid oxidation disorders in intact cultured fibroblasts. Adv Exp Med Biol. 1999;466:321–325. doi: 10.1007/0-306-46818-2_37. [DOI] [PubMed] [Google Scholar]
  12. Pollitt R. J., Green A., McCabe C. J., Booth A., Cooper N. J., Leonard J. V., Nicholl J., Nicholson P., Tunaley J. R., Virdi N. K. Neonatal screening for inborn errors of metabolism: cost, yield and outcome. Health Technol Assess. 1997;1(7):i-iv, 1-202. [PubMed] [Google Scholar]
  13. Pollitt R. J., Leonard J. V. Prospective surveillance study of medium chain acyl-CoA dehydrogenase deficiency in the UK. Arch Dis Child. 1998 Aug;79(2):116–119. doi: 10.1136/adc.79.2.116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sim K. G., Wiley V., Carpenter K., Wilcken B. Carnitine palmitoyltransferase I deficiency in neonate identified by dried blood spot free carnitine and acylcarnitine profile. J Inherit Metab Dis. 2001 Feb;24(1):51–59. doi: 10.1023/a:1005606805951. [DOI] [PubMed] [Google Scholar]
  15. Tanaka K., Gregersen N., Ribes A., Kim J., Kølvraa S., Winter V., Eiberg H., Martinez G., Deufel T., Leifert B. A survey of the newborn populations in Belgium, Germany, Poland, Czech Republic, Hungary, Bulgaria, Spain, Turkey, and Japan for the G985 variant allele with haplotype analysis at the medium chain Acyl-CoA dehydrogenase gene locus: clinical and evolutionary consideration. Pediatr Res. 1997 Feb;41(2):201–209. doi: 10.1203/00006450-199702000-00008. [DOI] [PubMed] [Google Scholar]
  16. Tanner S., Sharrard M., Cleary M., Walter J., Wraith E., Lee P., Leonard J., Morris A., McIntosh N. Screening for medium chain acyl-CoA dehydrogenase deficiency has still not been evaluated. . BMJ. 2001 Jan 13;322(7278):112–112. [PMC free article] [PubMed] [Google Scholar]
  17. Touma E. H., Charpentier C. Medium chain acyl-CoA dehydrogenase deficiency. Arch Dis Child. 1992 Jan;67(1):142–145. doi: 10.1136/adc.67.1.142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Wilcken B., Carpenter K. H., Hammond J. Neonatal symptoms in medium chain acyl coenzyme A dehydrogenase deficiency. Arch Dis Child. 1993 Sep;69(3 Spec No):292–294. doi: 10.1136/adc.69.3_spec_no.292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wilcken B., Hammond J., Silink M. Morbidity and mortality in medium chain acyl coenzyme A dehydrogenase deficiency. Arch Dis Child. 1994 May;70(5):410–412. doi: 10.1136/adc.70.5.410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wiley V., Carpenter K., Wilcken B. Newborn screening with tandem mass spectrometry: 12 months' experience in NSW Australia. Acta Paediatr Suppl. 1999 Dec;88(432):48–51. doi: 10.1111/j.1651-2227.1999.tb01157.x. [DOI] [PubMed] [Google Scholar]
  21. Wiltshire E. J., Poplawski N. K., Harrison J. R., Fletcher J. M. Treatment of late-onset nonketotic hyperglycinaemia: effectiveness of imipramine and benzoate. J Inherit Metab Dis. 2000 Feb;23(1):15–21. doi: 10.1023/a:1005690611675. [DOI] [PubMed] [Google Scholar]
  22. Ziadeh R., Hoffman E. P., Finegold D. N., Hoop R. C., Brackett J. C., Strauss A. W., Naylor E. W. Medium chain acyl-CoA dehydrogenase deficiency in Pennsylvania: neonatal screening shows high incidence and unexpected mutation frequencies. Pediatr Res. 1995 May;37(5):675–678. doi: 10.1203/00006450-199505000-00021. [DOI] [PubMed] [Google Scholar]

Articles from Archives of Disease in Childhood. Fetal and Neonatal Edition are provided here courtesy of BMJ Publishing Group

RESOURCES