SUDDEN INFANT DEATH AND LONG-CHAIN 3-HYDROXYACYL-CoA DEHYDROGENASE

Wanders, Ronald J. A.; Durán, Marinus; IJlst, Lodewijk; Jager, J. P. de; Gennip, A. H. van; Jakobs, C.; Dorland, L.; Sprang, F. J. van

doi:10.1016/s0140-6736(89)90300-0

Cited by 123 publications

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“…Two previous cases of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency have been reported (8)(9)(10)22). One child was well until 9 mo of age when he developed an illness characterized by vomiting, listlessness and hypotonia after a respiratory infection.…”

Section: Discussionmentioning

confidence: 99%

“…The biochemical defect in this patient is presumably the same as that in her twin brother. Another child presented at the age of 5 mo when after a few days of vomiting and diarrhea she became lethargic, associated with hypoketotic hypoglycemia and a massive 3-hydroxy dicarboxylic aciduria (8,9). She recovered rapidly after i.v.…”

Section: Discussionmentioning

confidence: 99%

“…The membrane-associated higher molecular weight enzyme has greater activity to the longchain substrates, whereas the enzyme with maximum activity for the short-chain substrates appears to be in the mitochondrial matrix. There have only been two previous reports of defects of the long-chain 3-hydroxyacyl-CoA dehydrogenase (8)(9)(10). We describe the clinical and biochemical features of two children who had severe hypoglycemia, metabolic acidosis, and lipid storage due to a defect of long-chain 3-hydroxyacyl-CoA dehydrogenase.…”

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Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency

et al. 1991

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ABSTRACT. We describe the clinical features and biochemical findings of two patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Both children presented with an acute metabolic crisis. Both had hypoglycemia and excreted even-chain unsubstituted dicarboxylic and 3-hydroxy-dicarboxylic acids in the urine. Measurement of the enzymes of fatty acid oxidation in cultured skin fibroblasts showed low activity of long-chain 3-hydroxyacyl-CoA dehydrogenase, but normal activity of short-chain 3-hydroxyacyl-CoA dehydrogenase. The defect was further characterized by immunoprecipitating the short-chain enzyme using monospecific antibodies. It is probably inherited as an autosomal recessive trait, inasmuch as intermediate enzyme activity was found in the fibroblasts from the parents of one child. (Pediatr Res 29: 406-411,1991) Abbreviations NR, normal range ETF, electron transfer flavoprotein CTP, carnitine palmitoyltransferase oxoacyl-CoA thiolases. ETF and ETF:ubiquinone oxidoreductase transfer electrons from the acyl-CoA dehydrogenases to the respiratory chain. All these enzymes are required for the complete oxidation of long-chain fatty acids. Defects of several enzymes of @-oxidation have been described in detail, and these include abnormalities of short-chain (3), medium-chain (4), and longchain (5) acyl-CoA dehydrogenases, ETF, and ETF dehydrogenase (6).The 3-hydroxyacyl-CoA dehydrogenases catalyze the reversible dehydrogenation of 3-hydroxyacyl-CoA to 3-ketoacyl-CoA. In mitochondria, there appear to be two enzymes that have different substrate specificities (7). The membrane-associated higher molecular weight enzyme has greater activity to the longchain substrates, whereas the enzyme with maximum activity for the short-chain substrates appears to be in the mitochondrial matrix. There have only been two previous reports of defects of the long-chain 3-hydroxyacyl-CoA dehydrogenase (8-10). We describe the clinical and biochemical features of two children who had severe hypoglycemia, metabolic acidosis, and lipid storage due to a defect of long-chain 3-hydroxyacyl-CoA dehydrogenase. CASE REPORTFatty acids are an essential metabolic fuel, particularly at times of stress or prolonged fasting. They are predominantly metabolized in the mitochondria, and defects of mitochondrial fatty acid oxidation are increasingly recognized as an important group of inborn errors of metabolism that can cause sudden infant death syndrome ("cot death"), Reye's syndrome, hypoketotic hypoglycemic coma, and muscle weakness (1).Mitochondria1 p-oxidation requires activation of fatty acids by long-chain acyl-CoA synthetase to form the fatty acyl-CoA ester. The acyl groups are then transferred into the mitochondrial matrix by the concerted action of CPT I, carnitineacylcarnitine translocase, and CPT 11. Acyl-CoA esters then undergo 0-oxidation by a repeated sequence of flavoprotein-linked dehydrogenation, hydration, NAD'-linked dehydrogenation, and thiolysis to generate acetyl-CoA (2). There are two or three enzymes with overlappin...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency

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“…A reduction in activity of the long-chain HAD in fibroblast homogenates has been proved in 6 cases (Wanders et al, 1989;Dionisi Vici et al, 1990;Hale et al, 1990;Rocchiccioli et al, 1990). In one patient a reduction in the activity of short-chain HAD has been found (Hale and Thorpe, 1989).…”

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“…3-Hydroxyacyl-CoA dehydrogenase (HAD) deficiency (EC 1.1.1.35) as a cause of 3-hydroxydicarboxylicaciduria has been suspected in approximately 30 cases (Riudor et al, 1986;Kelley and Morton, 1988;Poll-The et al, 1988;Hale and Thorpe, 1989;Wanders et al, 1989;Dionisi Vici et al, 1990;Hagenfeldt et al, 1990;Hale et al, 1990;Pollitt, 1990). A reduction in activity of the long-chain HAD in fibroblast homogenates has been proved in 6 cases (Wanders et al, 1989;Dionisi Vici et al, 1990;Hale et al, 1990;Rocchiccioli et al, 1990).…”

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Long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency

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Jakobs

IJlst

et al. 1991

J of Inher Metab Disea

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Fatty Acid Oxidation Disorders

Polinati

Eskelin

Tyni

2009

Encyclopedia of Life Sciences

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Mitochondrial fatty acid oxidation (FAO) is a major energy‐providing pathway under conditions of prolonged fasting, exercise or metabolic stress. A number of inherited disorders affecting this metabolic pathway have been known for almost two decades. Defects of mitochondrial FAO characteristically present with severe metabolic crises associated with low blood glucose (hypoglycaemia) during infancy and childhood and are also a relatively frequent cause of muscle diseases and cardiac muscle disease. The symptoms are typically episodic and often associated with mild viral infections or fasting. Therapeutic interventions are generally effective in preventing metabolic decompensation, which emphasizes the importance of early diagnosis. Diagnostic testing, determining optimal dietary regimens for each disorder and prenatal screening for these disorders may essentially alter an otherwise poor prognosis for many patients with FAO disorders. Key Concepts: Fatty acids can be oxidized by α‐oxidation in peroxisomes, by β‐oxidation in mitochondria and peroxisomes, and ω‐oxidation in the endoplasmic reticulum. Mitochondrial FAO is a major energy‐providing pathway under conditions of prolonged fasting, exercise or metabolic stress. A single β‐oxidation cycle consists of a series of four repeated enzymatic steps: dehydrogenation (oxidation), hydration, a second dehydrogenation and thiolytic cleavage of the carbon chain. Mitochondrial FAO defects present with severe metabolic crises associated with nonketotic hypoglycaemia, fatty liver, muscle weakness and cardiomyopathy. As a group, mitochondrial FAO defects are among the most common autosomal recessively inherited metabolic disorders. The main objective of therapeutic intervention is to secure sufficient caloric intake during periods of metabolic stress and fasting, and prevent accumulation of β‐oxidation intermediates. Neonatal screening of FAO disorders has been initiated in several countries worldwide, improving the opportunities for early dietary therapies.

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SUDDEN INFANT DEATH AND LONG-CHAIN 3-HYDROXYACYL-CoA DEHYDROGENASE

Cited by 123 publications

References 2 publications

Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency

Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency

Long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency

Fatty Acid Oxidation Disorders

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