Hypoglycemia, Hepatic Dysfunction, Muscle Weakness, Cardiomyopathy, Free Carnitine Deficiency and Long-Chain Acylcarnitine Excess Responsive to Medium Chain Triglyceride Diet

Glasgow, Allen M.; Engel, Andrew G.; Bier, Dennis M.; Perry, Lowell W.; Dickie, Mary; Todaro, Jane; Brown, Barbara I.; Utter, Merton F.

doi:10.1203/00006450-198305000-00003

Cited by 81 publications

(19 citation statements)

References 34 publications

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“…Similar beneficial effects of an MCT diet were reported by Glasgow et al [7] in a patient with an apparent defect of long-chain fatty acid [3-oxidation. This patient also accumulated long-chain acylcarnitine in muscle and plasma, as did our patient.…”

Section: Discussionsupporting

confidence: 76%

3-Hydroxydicarboxylic aciduria due to long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency associated with sudden neonatal death: protective effect of medium-chain triglyceride treatment

et al. 1991

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Two siblings were found to be affected by long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, one of which died suddenly and unexpectedly on the 3rd day of life suffering from extreme hypoketotic hypoglycaemia. The younger sibling started to have feeding problems, lowered consciousness, and liver dysfunction at the age of 5 months. Her urine contained large amounts of C6-C14 3-hydroxydicarboxylic acids and conjugated 3-hydroxyoctanoic acid, as verified by gas chromatography/mass spectrometry. Plasma long-chain acylcarnitine was increased. A clue to the diagnosis was given by the results of a phenylpropionic acid loading test. This revealed small, but significant amounts of conjugated 3-hydroxyphenylpropionic acid (phenylhydracrylic acid) in the patient's urine. Subsequently, the activity of long-chain 3-hydroxyacyl-CoA dehydrogenase was found to be deficient in cultured skin fibroblasts. Based on the findings obtained by a medium-chain triglyceride load, a diet enriched in this type of fat was prescribed. On this regimen the patient started to thrive, signs of cardiomyopathy disappeared, and her liver function normalized.

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Section: Discussionsupporting

confidence: 76%

3-Hydroxydicarboxylic aciduria due to long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency associated with sudden neonatal death: protective effect of medium-chain triglyceride treatment

et al. 1991

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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: 92%

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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“…In addition to the C6 to C10 dicarboxylic aciduria observed in most, if not all (8,20), reported cases of deficient P-oxidation, our patient excreted longer-chain C,2 and C I 4 dicarboxylic acids with a hydroxyl group in 3-position. These compounds, not found in patients with LCAD deficiency, were reported in the urine of one patient with similar clinical presentation (8), who was proven subsequently to have a defect in fatty acid oxidation at the level of long-chain 3-hydroxyacyl-CoA dehydrogenation (20).…”

Section: Discussionmentioning

confidence: 98%

Deficiency of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase: A Cause of Lethal Myopathy and Cardiomyopathy in Early Childhood

et al. 1990

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ABSTRACT. A child presented in early childhood with episodes of coma and hypoglycemia and a rapidly evolutive myopathy and cardiomyopathy leading to death at 9 mo of age. Ketosis was decreased (blood P-hydroxybutyrate: 0.07 mmol/L) despite normal plasma levels of fatty acids (0.81 mmol/L). The patient's urine contained excessive amounts of the Cs to Clo dicarboxylic acids present in almost all defects of fatty acid mitochondrial oxidation. More specifically, gas chromatography-mass spectrometry identified an accumulation of medium-and long-chain (Cs to C14) 3-hydroxy-dicarboxylic acids, suggesting a defect of the mitochondrial enzyme that normally dehydrogenates these 3-hydroxyacyl-CoA esters. Biochemical studies in the patient's cultured fibroblasts confirmed the impairment of medium-and long-chain fatty acid oxidation, and allowed the recognition of the deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase. The activities of long-, medium-, and short-chain acyl-CoA dehydrogenases and 3-ketoacylCoA thiolase were normal. These results describe a disorder of fatty acid metabolism that affects the liver, skeletal muscles, and myocardium. It is important to point out that long-chain 3-hydroxyacyl-CoA deficiency shares many clinical similarities with systemic carnitine deficiency, as well as with carnitine-palmityl-CoA transferase and longchain acyl-CoA dehydrogenase deficiencies. The differential diagnosis of this disease relies on the demonstration of long-chain urinary dicarboxylic acids with a hydroxyl group in 3-position and the study of the enzyme activity in cultured fibroblasts. (Pediatr Res 28: 657-662, 1990)

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Hypoglycemia, Hepatic Dysfunction, Muscle Weakness, Cardiomyopathy, Free Carnitine Deficiency and Long-Chain Acylcarnitine Excess Responsive to Medium Chain Triglyceride Diet

Cited by 81 publications

References 34 publications

3-Hydroxydicarboxylic aciduria due to long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency associated with sudden neonatal death: protective effect of medium-chain triglyceride treatment

3-Hydroxydicarboxylic aciduria due to long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency associated with sudden neonatal death: protective effect of medium-chain triglyceride treatment

Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency

Deficiency of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase: A Cause of Lethal Myopathy and Cardiomyopathy in Early Childhood

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