Correspondence

Medium Chain Acyl–Coenzyme A Dehydrogenase Deficiency in a Neonate

N Engl J Med 2007; 357:1781October 25, 2007

Article

To the Editor:

Medium-chain acyl–coenzyme A dehydrogenase (MCAD) deficiency is the most frequently diagnosed defect in mitochondrial beta-oxidation, with a prevalence of 1 case per 15,000 persons in the United States.1 Since patients with MCAD deficiency typically present at 3 to 24 months of age with an unanticipated episode of life-threatening, hypoketotic hypoglycemia, the disease has been a prime impetus for the screening of newborns' blood with tandem mass spectroscopy, a major new public health initiative.

We report on a 3-day-old neonate with lethargy, ketotic hypoglycemia, and poor feeding; incessant ventricular tachyarrhythmia developed, which progressed to episodes of torsades de pointes that were refractory to multiple antiarrhythmic medications. With extracorporeal life support and the addition of carnitine, glucose, and insulin, the patient's condition improved quickly. The initial newborn screening blood test, performed at 42 hours of age, showed elevations in medium-chain acylcarnitine levels that were consistent with MCAD deficiency, but the results were not reported until after the initial presentation. Molecular testing revealed that the patient was homozygous for the common A985G mutation.

At first, the diagnosis of MCAD deficiency was not considered, probably because the disease is usually not diagnosed in newborns. However, neonatal presentation has been well documented. Wilcken et al.2 reported that 40% of children (8 of 20) who presented clinically with MCAD deficiency had had neonatal symptoms. In the United Kingdom, 7 of 73 patients who presented clinically with confirmed or suspected MCAD deficiency had a neonatal presentation, and 3 patients presented at 2 days of age.3 A Dutch retrospective study showed that 15 of 155 patients with the disease had presented at 4 days of age or younger.4

The atypical presentation of MCAD deficiency in the newborn period and its successful treatment have important implications for the conduct of newborn screening programs and medical management of MCAD deficiency in newborns. Early diagnosis and initiation of treatment probably would have prevented severe cardiac sequelae in our patient. The possibility of a newborn presentation raises the question of whether a more expedited screening process should be instituted, with a blood sample obtained at 24 hours of age and the results available and communicated to the physician by 3 days of age. The quick reversibility of our patient's cardiac problems highlights the potential benefit of prompt diagnosis and treatment.

Gregory Rice, M.D.
Thomas Brazelton, III, M.D., M.P.H.
Kathleen Maginot, M.D.
Shardha Srinivasan, M.D.
Gregory Hollman, M.D.
Jon A. Wolff, M.D.
University of Wisconsin School of Medicine and Public Health, Madison, WI 53706

4 References

1. 1

   Andresen BS, Dobrowolski SF, O'Reilly L, et al. 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 2001;68:1408-1418
   CrossRef | Web of Science | Medline

2. 2

   Wilcken B, Hammond J, Silink M. Morbidity and mortality in medium-chain acyl coenzyme A dehydrogenase deficiency. Arch Dis Child 1994;70:410-412
   CrossRef | Web of Science | Medline

3. 3

   Pollitt RJ, Leonard JV. Prospective surveillance study of medium-chain acyl-CoA dehydrogenase deficiency in the UK. Arch Dis Child 1998;79:116-119
   CrossRef | Web of Science | Medline

4. 4

   Derks TG, Reijngoud DJ, Waterham HR, et al. The natural history of medium-chain acyl CoA dehydrogenase deficiency in the Netherlands: clinical presentation and outcome. J Pediatr 2006;148:665-670
   CrossRef | Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   Marcello Marcì, Patrizia Ajovalasit. (2009) Medium-Chain Acyl-CoA Dehydrogenase Deficiency in an Infant with Dilated Cardiomyopathy. Cardiology Research and Practice 2009, 1-3
   CrossRef

2. 2

   (2008) More on Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency in a Neonate. New England Journal of Medicine 358:6, 647-647
   Full Text

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