Summary
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.
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Abbreviations
- MCAD:
-
medium-chain acyl-CoA dehydrogenase
- 3MCCC:
-
3-methylcrotonyl-CoA carboxylase
- PKU:
-
phenylketonuria
References
American College of Medical Genetics (2006) Newborn screening: towards a uniform screening panel and system. Genet Med 8: 1S–252S.
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.
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].
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.
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.
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.
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.
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.
Ficicioglu C, Payan I (2006) 3-Methylcrotonyl-CoA carboxylade deficiency: metabolic decompensation in a noncompliant child detected through newborn screening. Pediatrics 118: 2555–2556.
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.
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.
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.
Pearson MA, Aleck KA, Heidenreich RA (1995) Benign clinical presentation of 3-methylcrotonylglycinuria. J Inherit Metab Dis 18: 640–641.
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.
Pollitt RJ (2007) Introducing new screens: why are we all doing different things? J Inherit Metab Dis 30: 423–429.
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.
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.
Steen C, Baumgartner ER, Duran M, et al (1999) Metabolic stroke in isolated 3-methycrotonyl-CoA carboxylase deficiency. Eur J Pediatr 158: 730–733.
Tanaka K, Yokota I, Coates PM, et al (1992) Mutations in the medium chain acyl-CoA dehydrogenase (MCAD) gene. Hum Mutat 1: 271–279.
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.
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.
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.
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.
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.
Wilson JMG, Jungner G (1968) Principles and Practice of Screening for Disease, Geneva: World Health Organization.
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.
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.
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.
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.
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Communicating editor: Rodney Pollitt
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Wilcken, B. The consequences of extended newborn screening programmes: Do we know who needs treatment?. J Inherit Metab Dis 31, 173–177 (2008). https://doi.org/10.1007/s10545-008-0843-8
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DOI: https://doi.org/10.1007/s10545-008-0843-8