Frequency of Medium-Chain Acyl-CoA Dehydrogenase Deficiency G-985 Mutation in Sudden Infant Death Syndrome

Abstract

ABSTRACT. A small percentage of apparent sudden infant death syndrome (SIDS) victims may have an unsuspected metabolic disorder. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a disorder of fatty acid oxidation that has been the most common such metabolic disorder found in series of SIDS victims. A single mutation in MCAD deficiency has been recently described (G-985) that accounts for approximately 90% of MCAD deficiency mutations. We studied the hypothesis that heterozygosity or homozygosity for this specific MCAD deficiency mutation might be associated with SIDS. DNA was extracted from the paraffin-embedded autopsy tissues of 67 victims of SIDS in Monroe County, NY who died between 1984 and 1989. Using the polymerase chain reactionlNco1 digestion method, we found no (2-985 homozygotes and three (4.5%) G-985 heterozygotes. In 70 newborn controls, there were no G-985 homozygotes and one (1.4%) heterozygote. Although the frequency of G-985 heterozygotes was slightly greater than in our control group, it was not statistically different. We conclude that the specific MCAD deficiency mutation G-985 is not strongly associated with SIDS and that MCAD deficiency probably does not make a significant contribution to the etiology of SIDS. retrospective study of 200 infants in England who unexpectedly died showed that 14 (7%) had microscopic evidence of fatty changes in various tissues, suggesting a disorder of fatty acid oxidation (2). Enzyme analysis of tissues in nine of these 14 cases showed three cases of MCAD deficiency and one case of longchain acyl-CoA dehydrogenase deficiency. This observation and similar observations by others have suggested that fatty acid oxidation defects should be considered in any infant that dies with SIDS or in any baby or child who has an unexpected death (3, 4). There is controversy, however, as to whether fatty acid oxidation defects are present in increased frequency in SIDS (5). 30MCAD deficiency is the most common enzyme deficiency in fatty acid oxidation (6). Affected children usually present within the first 2 y of life with recurrent episodes of hypoglycemia that are brought on by poor nutritional intake often associated with a respiratory or gastrointestinal viral infection. Affected children often present in a coma or with an altered level of consciousness. The striking laboratory abnormality is that despite the hypoglycemia these children have a trace of or no ketone bodies in their urine. The inability to make ketone bodies reflects their inability to metabolize medium-chain fatty acids. Approximately 25% of affected children die during their initial presentation (6). Between episodes of illness, the children are clinically normal and healthy. MCAD deficiency is an autosomal recessive disorder, so there is sometimes an affected sibling.The molecular basis of MCAD deficiency mutations was recently described by Matsubara et al. (7) and Yokota et al. (8). Each showed that there was one prevalent mutation in documented cases of MCAD deficiency, an A to G mutation at po...

Medium-chain acyl-CoA dehydrogenase deficiency does not correlate with apparent life-threatening events and the sudden infant death syndrome: results from phenylpropionate loading tests and DNA analysis

“…Later when genetic analysis became available, 142 SIDS victims were screened for the presence of the A985G mutation. While this study was in progress, results from similar genetic studies in other countries have been presented [2,7,8,9,22,25,26,28]. Our data indicate that MCAD deficiency is not major cause of ALTE and, in agreement with the results from the other studies, its frequency is not increased in children who died of SIDS.…”

Gene variants predisposing to SIDS: current knowledge

“…The most prevalent mutation causing MCAD deficiency is A985G, and this mutation has been investigated in at least nine studies including 2587 SIDS cases and 4636 controls [90][91][92][93][94][95][96][97][98]. In this series 16 SIDS cases had the A985G mutation (0.6%), and only two of the cases were homozygous for the mutation, and thus had MCAD deficiency as the cause of death.…”

Data required for the evaluation of newborn screening programmes

“…The published data on the absence of an association between MCADD and sudden infant death syndrome [3,9,14,16] do not solve the issue because most serious metabolic decompensations in MCADD are observed beyond the 1st year of life [18]. Such data could be generated by analyses of the Guthrie cards of children with infant death recorded in categories compatible with death during acute metabolic decompensation.…”