Neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency

Abstract

We support Morteza Pourfarzam and colleagues' hope1Pourfarzam M Morris A Appleton M Craft A Bartlett K Neonatal screening for medium chain acyl-coA dehydrogenase deficiency.Lancet. 2001; 358: 1063-1064Summary Full Text Full Text PDF PubMed Scopus (77) Google Scholar that screening for MCAD deficiency will become more widely introduced in neonatal genetic and metabolic screening programmes. Testing requires a heel-prick filter paper neonate sample, routinely taken for other testing, which can be analysed in one assay by tandem mass spectrometry. As the researchers mention, mortality and morbidity in undiagnosed MCAD deficiency is high. There is also a high incidence (20%) of previous sibling deaths.2Wilson CJ Champion MP Collins JE Clayton PT Leonard JV Outcome of medium chain acyl-CoA dehydrogenase deficiency after diagnosis.Arch Dis Child. 1999; 80: 459-462Crossref PubMed Scopus (85) Google Scholar The first crisis is fatal in up to 25% of cases, and survivors frequently having residual neurological damage. The first episode may be misdiagnosed as sudden infant death syndrome or an encephalopathic syndrome, such as Reyes; other patients may present with learning difficulties in later childhood. Management is simple and effective—avoidance of fasting stress by glucose or carbohydrate intake and possible carnitine supplementation. Diagnosis has implications for future pregnancies and preimplantation diagnosis is now possible as a clinical service.3Ioulianos A Wells D Harper JC Delhanty JDA A successful strategy for preimplantation diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.Prenat Diagn. 2000; 20: 593-598Crossref PubMed Scopus (17) Google Scholar Although Pourfarzam and colleagues' study is retrospective, prospective studies are in progress. The New England Screening Programme4New England Newborn Screening Program.www.umassmed.edu/nbs/Google Scholar (Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont) screens for ten disorders. Cystic fibrosis and 19 additional metabolic disorders are being screened in a pilot programme that includes two of the states (Massachusetts and Maine). A prospective study is currently comparing the results in children identified through the new expanded neonatal screening programme in Maine and Massachusetts and children identified clinically in the other New England states. In the New England Program, more than 160 000 neonates have been screened by tandem mass spectrometry.5Zytkovicz TH Fitzgerald EF Marsden D et al.Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: a two-year summary from the New England Newborn Screening Program.Clin Chem. 2001; 47: 1945-1955Crossref PubMed Scopus (420) Google Scholar Ten infants with MCAD deficiency were identified as well as ten with other fatty acid and organic acid disorders, and 22 babies with aminoacid disorders. In addition to this increased coverage of metabolic disorders, one tandem mass spectrometry analysis displaces the multiple Guthrie bacterial assays traditionally used in neonatal screening. The importance of screening is that the much wider coverage of metabolic disorders, such as MCAD deficiency, allows for immediate diagnosis, a reduction in parental stress, planned management (feeding, biochemical monitoring, special formulas or medications and developmental services), and other measures that should lead to more favourable outcomes.