Document Detail


Sudden death in medium chain acyl-coenzyme a dehydrogenase deficiency (MCADD) despite newborn screening.
MedLine Citation:
PMID:  20580581     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is the most frequent of the fatty acid oxidation disorders (FAOD), a group caused by defects in the mitochondrial B-oxidation of fatty acids. Fatty acid oxidation is critical in supplying energy during periods when glucose is limited or when energy needs are increased beyond the availability of glucose. In MCADD, this energy shortage can result in acute metabolic episodes or sudden death. The prevention of sudden death from MCADD served as the primary impetus to expand newborn screening. However, we have experienced sudden death in four children with MCADD despite their detection by newborn screening. The purpose of this report is to alert others to the danger of sudden death in MCADD even when it is detected by newborn screening, to identify the clinical symptoms that precede sudden death, and to examine the relationship between the newborn screening result and the risk for sudden death.
METHODS: We describe these children and their metabolic findings with emphasis on their newborn screening octanoylcarnitine (C8) level, the primary marker for newborn detection of MCADD. We also performed a literature search of cases of sudden death in MCADD in which the clinical status preceding death is described.
RESULTS: The newborn screening C8 levels in our four cases were markedly elevated, ranging from 8.4 to 24.8micromol/L (cut off<0.8micromol/L). Only two of the children were homozygous for the common c.985A>G MCAD mutation; the other two were heterozygous for this mutation. Similarly, among the eight reported cases which included MCAD genotypes, five were homozygous for the c.985A>G mutation, while two were heterozygous and one was homozygous for a splice site mutation. Vomiting 12-24h before sudden death was present in all four of our cases, and the review of reported cases of sudden death in MCADD disclosed vomiting as a frequent symptom.
CONCLUSION: We suggest that in MCADD (1) a newborn screening C8 level of 6micromol/L or greater represents particular risk of sudden death; (2) that MCAD genotypes other than homozygosity for the c.985A>G mutation are also associated with sudden death; (3) that vomiting is a frequent symptom preceding sudden death; and (4) social support and medical follow-up of these families are crucial in reducing the occurrence of sudden death.
Authors:
Roman Yusupov; David N Finegold; Edwin W Naylor; Inderneel Sahai; Susan Waisbren; Harvey L Levy
Publication Detail:
Type:  Case Reports; Journal Article     Date:  2010-06-09
Journal Detail:
Title:  Molecular genetics and metabolism     Volume:  101     ISSN:  1096-7206     ISO Abbreviation:  Mol. Genet. Metab.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-16     Completed Date:  2011-01-24     Revised Date:  2011-12-06    
Medline Journal Info:
Nlm Unique ID:  9805456     Medline TA:  Mol Genet Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  33-9     Citation Subset:  IM    
Affiliation:
Division of Genetics, Children's Hospital Boston, Boston, MA 02115, USA. romanyu1@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Acyl-CoA Dehydrogenase / blood,  deficiency,  genetics,  metabolism
Child, Preschool
Death, Sudden*
Female
Homozygote
Humans
Infant
Infant, Newborn
Lipid Metabolism, Inborn Errors* / blood,  diagnosis,  metabolism
Male
Mutation
Neonatal Screening*
Chemical
Reg. No./Substance:
EC 1.3.99.3/Acyl-CoA Dehydrogenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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