Correspondence

More on Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency in a Neonate

N Engl J Med 2008; 358:647February 7, 2008

Article

To the Editor:

Rice and colleagues (Oct. 25 issue)1 report a severe neonatal presentation of medium-chain acyl–coenzyme A dehydrogenase (MCAD) deficiency and suggest that newborn screening results should be communicated by 72 hours of age. In practice, it is unlikely that newborn screening, however timely, could prevent such events. My colleagues and I documented fatal neonatal presentations in 4 of the 81 patients with MCAD deficiency who were born in Australia between 1994 and 2004.2 All died before 72 hours. Five babies in the cohort with other fatty acid–oxidation defects also died, between 22 and 65 hours of age.

Reporting all screening results by 72 hours of age appears to be virtually impossible. Samples are taken at 24 hours, leaving only 48 hours for transporting samples to the laboratory, assaying large batches, checking, reassaying, sending results, and finally, finding the baby. The risk that a baby with MCAD deficiency will die in the first 72 hours seems likely to be around 5%, or one case per 300,000 births. Maybe we need to acknowledge that these early-presenting babies cannot be saved by the screening process itself.

Bridget Wilcken, M.B., Ch.B.
Children's Hospital at Westmead, Sydney, NSW 2145, Australia
bridgetw@chw.edu.au

2 References

1. 1

   Rice G, Brazelton T III, Maginot K, Srinivasan S, Hollman G, Wolff JA. Medium chain acyl-coenzyme A dehydrogenase deficiency in a neonate. N Engl J Med 2007;357:1781-1781
   Full Text | Web of Science | Medline

2. 2

   Wilcken B, Haas M, Joy P, et al. Outcome of neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency in Australia: a cohort study. Lancet 2007;369:37-42
   CrossRef | Web of Science | Medline

Author/Editor Response

In response to Wilcken's letter, we agree that some neonates will present with severe manifestations of MCAD deficiency before it is possible to identify them by newborn screening. However, it is incumbent on screening programs to streamline the process in order to decrease the time from birth to the report of an abnormal result. By obtaining specimens at 24 to 48 hours of age (depending on the time of birth) and providing 7-days-a-week laboratory operation and overnight courier service (and educating hospitals not to batch specimens for shipping), it should be possible to provide reports within 50 to 74 hours. Thus, this response time will be within the necessary time frame to either prevent the onset of disease or favorably affect the disease course for many of the newborn presentations. Earlier identification in the child described would have probably prevented the complications. Depending on local clinical practices (e.g., the propensity to check blood glucose levels in sick newborns), expedited newborn screening is likely to provide the opportunity to avoid severe complications and death in other newborns.

Gary Hoffman, B.S.
Wisconsin State Laboratory of Hygiene, Madison, WI 53706

Gregory Rice, M.D.
Jon A. Wolff, M.D.
University of Wisconsin School of Medicine and Public Health, Madison, WI 53706
jwolff@wisc.edu

Citing Articles (2)

Citing Articles

1. 1

   Ulrich A. Schatz, Regina Ensenauer. (2010) The clinical manifestation of MCAD deficiency: challenges towards adulthood in the screened population. Journal of Inherited Metabolic Disease
   CrossRef

2. 2

   Bridget Wilcken. (2010) Fatty acid oxidation disorders: outcome and long-term prognosis. Journal of Inherited Metabolic Disease
   CrossRef