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Logo of archdischfnArchives of Disease in Childhood - Fetal & NeonatalVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Arch Dis Child Fetal Neonatal Ed. Sep 2001; 85(2): F105–F109.
PMCID: PMC1721303

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


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 [gt-or-equal, slanted] 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 [gt-or-equal, slanted] 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.

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Selected References

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  • Tanaka K, Gregersen N, Ribes A, Kim J, Kølvraa S, Winter V, Eiberg H, Martinez G, Deufel T, Leifert B, et al. 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. [PubMed]
  • Blakemore AI, Singleton H, Pollitt RJ, Engel PC, Kolvraa S, Gregersen N, Curtis D. Frequency of the G985 MCAD mutation in the general population. Lancet. 1991 Feb 2;337(8736):298–299. [PubMed]
  • Curtis D, Blakemore AI, Engel PC, 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. [PubMed]
  • Pollitt RJ, Leonard JV. Prospective surveillance study of medium chain acyl-CoA dehydrogenase deficiency in the UK. Arch Dis Child. 1998 Aug;79(2):116–119. [PMC free article] [PubMed]
  • Wilcken B, Carpenter KH, Hammond J. Neonatal symptoms in medium chain acyl coenzyme A dehydrogenase deficiency. Arch Dis Child. 1993 Sep;69(3 Spec No):292–294. [PMC free article] [PubMed]
  • Iafolla AK, Thompson RJ, Jr, Roe CR. Medium-chain acyl-coenzyme A dehydrogenase deficiency: clinical course in 120 affected children. J Pediatr. 1994 Mar;124(3):409–415. [PubMed]
  • Touma EH, Charpentier C. Medium chain acyl-CoA dehydrogenase deficiency. Arch Dis Child. 1992 Jan;67(1):142–145. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Heptinstall LE, Till J, Wraith JE, Besley GT. Common MCAD mutation in a healthy parent of two affected siblings. J Inherit Metab Dis. 1995;18(5):638–639. [PubMed]
  • Naylor EW, Chace DH. 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. [PubMed]
  • Pollitt RJ, Green A, McCabe CJ, Booth A, Cooper NJ, Leonard JV, Nicholl J, Nicholson P, Tunaley JR, Virdi NK. Neonatal screening for inborn errors of metabolism: cost, yield and outcome. Health Technol Assess. 1997;1(7):i–202. [PubMed]
  • 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]
  • Ziadeh R, Hoffman EP, Finegold DN, Hoop RC, Brackett JC, Strauss AW, Naylor EW. 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. [PubMed]
  • 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. [PubMed]
  • Gregersen N, Blakemore AI, Winter V, Andresen B, Kølvraa S, Bolund L, Curtis D, Engel PC. 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. [PubMed]
  • Olpin SE, Manning NJ, Pollitt RJ, Bonham JR, 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. [PubMed]
  • Sim KG, 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. [PubMed]
  • Christodoulou J, Hoare J, Hammond J, Ip WC, Wilcken B. Neonatal onset of medium-chain acyl-coenzyme A dehydrogenase deficiency with confusing biochemical features. J Pediatr. 1995 Jan;126(1):65–68. [PubMed]
  • Matsubara Y, Narisawa K, Tada K. Medium-chain acyl-CoA dehydrogenase deficiency: molecular aspects. Eur J Pediatr. 1992 Mar;151(3):154–159. [PubMed]
  • Wiltshire EJ, Poplawski NK, Harrison JR, Fletcher JM. Treatment of late-onset nonketotic hyperglycinaemia: effectiveness of imipramine and benzoate. J Inherit Metab Dis. 2000 Feb;23(1):15–21. [PubMed]
  • Andresen BS, Bross P, Udvari S, Kirk J, Gray G, Kmoch S, Chamoles N, Knudsen I, Winter V, Wilcken B, et al. 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. [PubMed]
  • Clayton PT, Doig M, Ghafari S, Meaney C, Taylor C, Leonard JV, Morris M, Johnson AW. Screening for medium chain acyl-CoA dehydrogenase deficiency using electrospray ionisation tandem mass spectrometry. Arch Dis Child. 1998 Aug;79(2):109–115. [PMC free article] [PubMed]

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