Journal of Inherited Metabolic Disease

, Volume 31, Issue 2, pp 173–177 | Cite as

The consequences of extended newborn screening programmes: Do we know who needs treatment?

SSIEM Symposium 2007


The development of an evidence base for newborn screening is especially difficult because of the rarity of disorders now detectable. One consequence of expanded newborn screening is that physicians are being called upon to manage asymptomatic babies with persistent biochemical disturbances that indicate likely enzyme deficiencies. Some of these may be very mild. There is not always agreement as to who should be treated. Particular problems are seen with disorders that were previously thought very rare but are now found frequently by newborn screening. Some of these disorders appear benign or nearly so, and in the present state of knowledge should clearly not be included in routine newborn screening panels.



medium-chain acyl-CoA dehydrogenase


3-methylcrotonyl-CoA carboxylase




  1. American College of Medical Genetics (2006) Newborn screening: towards a uniform screening panel and system. Genet Med 8: 1S–252S.CrossRefGoogle Scholar
  2. Andresen BS, Dobrowolski SF, O’Reilly L, et al (2001) Medium-chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-based prospective screening of newborns differ from those observed in patients with clinical symptoms: identification and characterization of a new, prevalent mutation that results in mild MCAD deficiency. Am J Hum Genet 68: 1408–1418.PubMedCrossRefGoogle Scholar
  3. Arnold GL, Koeberl DD, Matern D, et al (2008) A Delphi-based consensus clinical practice protocol for the diagnosis and management of 3-methylcrotonyl CoA carboxylase deficiency. Mol Genet Metab [In press].Google Scholar
  4. Bartlett K, Bennett MJ, Hill RP, Lashford LS, Pollitt RJ, Worth HG (1984) Isolated biotin-resistant 3-methylcrotonyl CoA carboxylase deficiency presenting with life-threatening hypoglycaemia. J Inherit Metab Dis 7: 182.PubMedCrossRefGoogle Scholar
  5. Baykal T, Gokcay GH, Ince Z, et al (2005) Consanguineous 3-methycrotonyl-CoA carboxylase deficiency: early-onset necrotizing encephalopathy with lethal outcome. J Inherit Metab Dis 28: 229–233.PubMedCrossRefGoogle Scholar
  6. Boneh A, Baumgartner M, Hayman M, Peters H (2005) Methylcrotonyl-CoA carboxylase (MCC) deficiency associated with severe muscle pain and physical disability in an adult. J Inherit Metab Dis 28: 1139–1140.PubMedCrossRefGoogle Scholar
  7. de Kremer RD, Latini A, Suormala T, et al (2002) Leukodystrophy and CSF purine abnormalities associated with isolated 3-methylcrotonyl-CoA carboxylase deficiency. Metab Brain Dis 17: 13–18.PubMedCrossRefGoogle Scholar
  8. Elpeleg ON, Havkin S, Barash V, Jakobs C, Glick B, Shalev RS (1992) Familial hypotonia of childhood caused by isolated 3-methylcrotonyl-coenzyme A carboxylase deficiency. J Pediatr 121: 407–410.PubMedCrossRefGoogle Scholar
  9. Ficicioglu C, Payan I (2006) 3-Methylcrotonyl-CoA carboxylade deficiency: metabolic decompensation in a noncompliant child detected through newborn screening. Pediatrics 118: 2555–2556.PubMedCrossRefGoogle Scholar
  10. Gibson KM, Bennett MJ, Naylor EW, Morton DH (1998) 3-Methylcrotonyl-coenzyme A carboxylase deficiency in Amish/Mennonite adults identified by detection of increased acylcarnitines in blood spots of their children. J Pediatr 132: 519–523.PubMedCrossRefGoogle Scholar
  11. Mourmans J, Bakkeren J, de Jong J, et al (1995) Isolated (biotin-resistant) 3-methylcrotonyl-CoA carboxylase deficiency: four sibs devoid of pathology. J Inherit Metab Dis 18: 643–645.PubMedCrossRefGoogle Scholar
  12. Oude Luttikhuis HG, Touati G, Rabier D, Williams M, Jakobs C, Saudubray JM (2005) Severe hypoglycaemia in isolated 3-methylcrotonyl-CoA carboxylase deficiency; a rare, severe clinical presentation. J Inherit Metab Dis 28: 1136–1138.PubMedCrossRefGoogle Scholar
  13. Pearson MA, Aleck KA, Heidenreich RA (1995) Benign clinical presentation of 3-methylcrotonylglycinuria. J Inherit Metab Dis 18: 640–641.PubMedCrossRefGoogle Scholar
  14. Pinto L, Zen P, Rosa R, et al (2006) Isolated 3-methylcrotonyl-coenzyme A carboxylase deficiency in a child with metabolic stroke. J Inherit Metab Dis 29: 205–206.PubMedCrossRefGoogle Scholar
  15. Pollitt RJ (2007) Introducing new screens: why are we all doing different things? J Inherit Metab Dis 30: 423–429.PubMedCrossRefGoogle Scholar
  16. Seymour CA, Thomason MJ, Chalmers RA, et al (2001) Newborn screening for inborn errors of metabolism: a systematic review. Health Technol Assess 1: 23–26.Google Scholar
  17. Stadler SC, Polanetz R, Maier EM, et al (2006) Newborn screening for 3-methylcrotonyl-CoA carboxylase deficiency: population heterogeneity of MCCA and MCCB mutations and impact on risk assessment. Hum Mutat 27: 748–759.PubMedCrossRefGoogle Scholar
  18. Steen C, Baumgartner ER, Duran M, et al (1999) Metabolic stroke in isolated 3-methycrotonyl-CoA carboxylase deficiency. Eur J Pediatr 158: 730–733.PubMedCrossRefGoogle Scholar
  19. Tanaka K, Yokota I, Coates PM, et al (1992) Mutations in the medium chain acyl-CoA dehydrogenase (MCAD) gene. Hum Mutat 1: 271–279.PubMedCrossRefGoogle Scholar
  20. Tuchman M, Berry SA, Thuy LP, Nyhan WL (2007) Partial methylcroyonyl-coenzyme A carboxylase deficiency in an infant with failure to thrive, gastrointestinal dysfunction, and hypertonia. Pediatrics 1993: 664–666.Google Scholar
  21. van Maldegem BT, Duran M, Wanders RJ, et al (2006) Clinical, biochemical, and genetic heterogeneity in short-chain acyl-coenzyme A dehydrogenase deficiency. JAMA 296: 943–952.PubMedCrossRefGoogle Scholar
  22. Visser G, Suormala T, Smit GP, et al (2000) 3-methylcrotonyl-CoA carboxylase deficiency in an infant with cardiomyopathy, in her brother with developmental delay and in their asymptomatic father. Eur J Pediatr 159: 901–904.PubMedCrossRefGoogle Scholar
  23. Waddell L, Wiley V, Carpenter KH, et al (2005) Medium-chain acyl-CoA dehydrogenase deficiency: genotype–biochemical phenotype correlations. Mol Genet Metab 87: 32–39.PubMedCrossRefGoogle Scholar
  24. Wilcken B, Haas M, Joy P, et al (2007) Outcome of neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency: a cohort study. Lancet 369: 37–42.PubMedCrossRefGoogle Scholar
  25. Wilson JMG, Jungner G (1968) Principles and Practice of Screening for Disease, Geneva: World Health Organization.Google Scholar
  26. Wisemann UN, Suormala T, Pfenninger J, Baumgartner ER (1998) Partial 3-methycrotonyl-CoA carboxylase deficiency in an infant with fatal outcome due to progressive respiratory failure. Eur J Pediatr 157: 225–229.CrossRefGoogle Scholar
  27. Yap S, Monavari AA, Thornton P, Naughten E (1998) Late-infantile 3-methylcrotonyl-CoA carboxylase deficiency presenting as global developmental delay. J Inherit Metab Dis 21: 175–176.PubMedCrossRefGoogle Scholar
  28. Yap S, Naughten E (1998) Homocystinuria due to cystathionine beta-synthase deficiency in Ireland: 25 years’ experience of a newborn screened and treated population with reference to clinical outcome and biochemical control. J Inherit Metab Dis 21: 738–747.PubMedCrossRefGoogle Scholar
  29. Yap S, Rushe H, Howard PM, Naughten ER (2001) The intellectual abilities of early-treated individuals with pyridoxine-nonresponsive homocystinuria due to cystathionine beta-synthase deficiency. J Inherit Metab Dis 24: 437–447.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.Biochemical Genetics and Newborn ScreeningThe Children’s Hospital at WestmeadWestmeadAustralia
  2. 2.The University of SydneySydneyAustralia

Personalised recommendations