Metabolic disease and sudden unexpected death

Abstract

We read with interest the report by Buchino et al1Buchino JJ Corey TS Montgomery V Sudden unexpected death in hospitalized children.J Pediatr. 2002; 140: 461-465Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar regarding sudden unexpected death (SUD) in hospitalized children. We found the report to be informative on a topic that has been previously ignored. Unfortunately, the authors overlooked one important category of disease that can cause SUD: metabolic diseases. Fatty acid oxidation disorders (FOD), for example, can present anytime from two days of life through adulthood. Presenting symptoms of FOD, such as lethargy and vomiting, are vague and the course can rapidly turn fatal without warning. In one FOD, medium chain acyl-CoA dehydrogenase deficiency (MCADD), mortality in the initial presentation is 19% to 33%.2Wilcox RL Nelson CC Stenzel P Steiner RD Postmortem screening for fatty acid oxidation disorders by analysis of Guthrie cards with tandem mass spectrometry in sudden unexpected death in infancy.J Pediatr. 2002; 141: 833-836Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 3Roe CR Ding J Mitochondrial fatty acid oxidation disorders.in: 8th ed. The metabolic and molecular basis of inherited disease. David McGraw Hill, New York2001: 2297-2318Google Scholar, 4Iafolla AK Thompson Jr, RJ Roe CR Medium-chain acyl-coenzyme A dehydrogenase deficiency: clinical course in 120 affected children.J Pediatr. 1994; 124: 409-415Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar We were recently consulted regarding an in-hospital SUD in a 2-day old, asymptomatic, term infant.2Wilcox RL Nelson CC Stenzel P Steiner RD Postmortem screening for fatty acid oxidation disorders by analysis of Guthrie cards with tandem mass spectrometry in sudden unexpected death in infancy.J Pediatr. 2002; 141: 833-836Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar The breast-feeding newborn was separated from her mother for approximately six hours during a tubal ligation. At 46 hours of life the infant was evaluated for an intermittent, high-pitched, expiratory grunt; the physical examination was normal. Three hours later, the infant's father brought her to the nurses' station pulseless and cyanotic, and resuscitation efforts were unsuccessful. Oregon has a protocol for investigation of SUD in infancy. Following the protocol, residual newborn screening Guthrie card sample was submitted for testing. Tandem mass spectrometry acylcarnitine analysis showed a pattern consistent with very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD), and fibroblast in vitro fatty acid oxidation probe confirmed the diagnosis. This case of VLCADD presenting as an in-hospital SUD, as well as published data showing a significant incidence of SUD from MCADD,3Roe CR Ding J Mitochondrial fatty acid oxidation disorders.in: 8th ed. The metabolic and molecular basis of inherited disease. David McGraw Hill, New York2001: 2297-2318Google Scholar, 4Iafolla AK Thompson Jr, RJ Roe CR Medium-chain acyl-coenzyme A dehydrogenase deficiency: clinical course in 120 affected children.J Pediatr. 1994; 124: 409-415Abstract Full Text Full Text PDF PubMed Scopus (247) Google Scholar, 5Wilcken B Hammond J Silink M Morbidity and mortality in medium chain acyl coenzyme A dehydrogenase deficiency.Arch Dis Child. 1994; 70: 410-412Crossref PubMed Scopus (82) Google Scholar, 6Brackett JC Sims HF Steiner RD Nunge M Zimmerman EM de Martinville B et al.A novel mutation in medium chain acyl-CoA dehydrogenase causes sudden neonatal death.J Clin Invest. 1994; 94: 1477-1483Crossref PubMed Scopus (40) Google Scholar underscores the importance of recognizing inherited metabolic diseases as a cause of SUD and the need for FOD (and possibly other metabolic diseases) to be included in any protocol for investigation of SUD in hospitalized children. We recently published a protocol to aid in the diagnosis of children dying of suspected metabolic disease, which could easily be adapted to look for metabolic diseases in cases of SUD in the hospital setting.7Steiner RD Cederbaum SD Laboratory evaluation of urea cycle disorders.J Pediatr. 2001; 138: S21-S29Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar