Sudden Infant Death Syndrome and Inherited Disorders of Fatty Acid β-Oxidation

Harpey, Jean-Paul; Charpentier, C.; Paturneau-Jouas, Marion

doi:10.1159/000243301

Cited by 48 publications

(19 citation statements)

References 19 publications

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“…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 …”

supporting

confidence: 70%

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

et al. 1992

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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...

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supporting

confidence: 70%

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

et al. 1992

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“…Thus, the level of odd-chain acylcarnitine (representing intermediates in the BCAA catabolism), such as C5, is lower because it reflects a switch in substrate preference in favor of fatty acid over BCAA rather than hypermetabolism. An altered acylcarnitine metabolism has been reported in the inherited deficiency of enzyme activities in ␤-oxidation, such as medium-chain acyl-CoA dehydrogenase deficiency (22)(23)(24)(25)(26)(27), verylong-chain acyl-CoA dehydrogenase deficiency (28), long-chain hydroxyacyl-CoA dehydrogenase deficiency (29), and systemic carnitine deficiency (28,(30)(31)(32). However, the acylcarnitine profile of V1aRϪ/Ϫ mice was different from the profiles of disorders including deficiencies in these enzymes.…”

Section: Discussionmentioning

confidence: 99%

Hypermetabolism of Fat in V1a Vasopressin Receptor Knockout Mice

Hiroyama

Aoyagi

Fujiwara

et al. 2007

Molecular Endocrinology

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[Arg8]Vasopressin (AVP) has an antilipolytic action on adipocytes, but little is known about the mechanisms involved. Here, we examined the involvement of the V1a receptor in the antilipolytic effect of AVP using V1a receptor-deficient (V1aR-/-) mice. The levels of blood glycerol were increased in V1aR-/- mice. The levels of ketone bodies, such as acetoacetic acid and 3-hydroxybutyric acid, the products of the lipid metabolism, were increased in V1aR-/- mice under a fasting condition. Triacylglyceride and free fatty acid levels in blood were decreased in V1aR-/- mice. Furthermore, measurements with tandem mass spectrometry determined that carnitine and acylcarnitines in serum, the products of beta-oxidation, were increased in V1aR-/- mice. Most acylcarnitines were increased in V1aR-/- mice, especially in the case of 2-carbon (C2), C10:1, C10, C14:1, C16, C18:1, and hydroxy-18:1-carbon (OH-C18:1)-acylcarnitines under feeding rather than under fasting conditions. The analysis of tissue C2-acylcarnitine level showed that beta-oxidation was promoted in muscle under the feeding condition and in liver under the fasting condition. An in vitro assay using brown adipocytes showed that the cells of V1aR-/- mice were more sensitive to isoproterenol for lipolysis. These results suggest that the lipid metabolism is enhanced in V1aR-/- mice. The cAMP level was enhanced in V1aR-/- mice in response to isoproterenol. The phosphorylation of Akt by insulin stimulation was reduced in V1aR-/- mice. These results suggest that insulin signaling is suppressed in V1aR-/- mice. In addition, the total bile acid, taurine, and cholesterol levels in blood were increased, and an enlargement of the cholecyst was observed in V1aR-/- mice. These results indicated that the production of bile acid was enhanced by the increased level of cholesterol and taurine. Therefore, these results indicated that AVP could modulate the lipid metabolism by the antilipolytic action and the synthesis of bile acid via the V1a receptor.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

Data required for the evaluation of newborn screening programmes

Liebl¹,

Nennstiel-Ratzel²,

Roscher³

et al. 2003

Eur J Pediatr

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Tandem mass spectrometry offers the chance to improve newborn screening (NBS) for phenylketonuria and to expand screening programmes at minimal additional costs. So far, however, there are only limited data available on the incidence of a broader range of disorders presently being considered, their natural course, the benefits achievable and potential harm associated with screening. Based on a literature search and experience from the Bavarian extended screening trial, these questions are addressed using medium-chain acyl-CoA dehydrogenase deficiency (MCADD) as an example. The data retrieved are sufficient for estimation of the incidence of MCADD cases identifiable by NBS and for diagnosis following clinical symptoms. Clinically detected cases ascertained by active surveillance in populations with highly developed and freely accessible health care systems consistently amount to only 33% of those identified by NBS. This difference cannot be explained by the difference in the proportion of the homozygous 985A-->G mutation, which accounts for about 50% of cases identified in NBS. Further research is needed to assess the contribution of MCADD to unexplained deaths in infancy. Retrospective cohort studies enrolling at least 500,000 children would allow for a more precise estimate of the natural course of disease in particular with regard to less severe adverse outcomes. The most relevant gap in knowledge concerns the long-term outcome of children identified following symptoms and by newborn screening. Since randomised controlled trials are unlikely to be feasible on this issue, a standardised documentation protocol should be implemented in follow-up studies for cases identified either by high risk screening or newborn screening. A proposal for the content of such observational studies is made.

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Sudden Infant Death Syndrome and Inherited Disorders of Fatty Acid β-Oxidation

Cited by 48 publications

References 19 publications

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

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

Hypermetabolism of Fat in V1a Vasopressin Receptor Knockout Mice

Data required for the evaluation of newborn screening programmes

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