Β-Hydroxy-Β-Methylglutaricaciduria PRESENTING AS REYE'S SYNDROME

Leonard, J. V.; Seakins, J. W. T.; Griffin, Nicole

doi:10.1016/s0140-6736(79)91137-1

Cited by 42 publications

(14 citation statements)

References 2 publications

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“…The stimulation of oxygen consumption by RS serum had been attributed to the oxidation of uric acid by uricase containing microbodies contaminating rat liver mitochondrial preparations (13 (32)(33)(34)(35)(36). Hydroxymethyl glutaryl CoA lyase deficiency (35,36), ethylmalonic adipicaciduria (37), and systemic carnitine deficiency (32,33), and some cases of medium-chain acyldehydrogenase deficiency (38,39) and glutaric aciduria (40) The stimulation of respiration and ultrastructural changes in isolated mitochondria suggests that a disturbance in fatty acid metabolism leading to the accumulation of dicarboxylic acids is closely associated with the illness and may potentiate the mitochondrial dysfunction in RS. This is supported not only by the presence in the serum and urine of dicarboxylic acids which are products of w-oxidation, but by the massive free fatty acidemia and fatty deposition of the viscera and by the correlation of plasma lactate and blood ammonia to the urinary excretion of ketones and dicarboxylic acids or to the concentration of serum dicarboxylic acids (Tonsgard, J. H., unpublished observation).…”

Section: Discussionmentioning

confidence: 99%

Effect of Reye's syndrome serum on isolated chinchilla liver mitochondria.

Tonsgard¹,

Getz²

1985

J. Clin. Invest.

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A general impairment of liver mitochondrial enzymes is central to Reye's syndrome (RS). The respiration of isolated liver mitochondria was measured after the addition of concentrated normal serum or RS serum derived from 12 patients. RS serum stimulates oxygen consumption in isolated rat liver mitochondria. This effect is due to (a) the oxidation of uric acid by peroxisomes contaminating the preparation and (b) a stimulation of mitochondrial respiration (1.05±0.14 nmol of 02/min * mg of protein; control 030±0.08 nmol 02/min. mg). The stimulation of respiration occurs in the presence of all respiratory substrates, is dependent on the amount of serum added, and represents an uncoupling of oxidative phosphorylation. RS serum reduces ATP formation by 15-76%. The uncoupling effect correlates with the amount of free fatty acid in the serum sample and resembles the effect induced by the addition of a dicarboxylic fatty acid. Dicarboxylic fatty acids, especially long-chain dicarboxylic acids, impair ATP formation. Dicarboxylic acids were found in the serum of all RS patients and comprised as much as 54% of the total serum free fatty acids. 90% of the serum dicarboxylic acids were of 16-18 carbon lengths. The amount of dicarboxylic acids in the RS serum corresponded directly with the reduction in ATP formation by the RS serum. This demonstrates that dicarboxylic acids occur in RS and may be important in the general impairment of mitochondrial function in RS and other disorders where they are present.

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Section: Discussionmentioning

confidence: 99%

Effect of Reye's syndrome serum on isolated chinchilla liver mitochondria.

Tonsgard¹,

Getz²

1985

J. Clin. Invest.

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“…A high incidence of consanguinity has been observed [43,44]. In one case (No 4) the parents were of Pakistani descent and reported to be first cousins once removed [32]. Another patient (No 14) was the product of the second uncomplicated pregnancy, labor and delivery of healthy Saudi Arabian first cousins [23].…”

Section: Geneticsmentioning

confidence: 99%

“…Within 24h this patient was comatose and hyperpneic. Multifocal convulsions were observed following hospital admission in one patient (No 4; [32]) while another patient (No 7) was macrocephalic and severely mentally retarded. On the 2nd day of life, another patient (No 8) displaying hypoglycemia [19] developed myoclonic jerks and respiratory distress.…”

mentioning

confidence: 98%

3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: review of 18 reported patients

1988

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3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA lyase) is an inborn error of leucine catabolism which often leads to life-threatening illness in the neonatal period. The cardinal clinical features include severe infantile hypoglycemia, metabolic acidosis, hepatomegaly, lethargy or coma and apnea. Hyperammonemia is variable. There is a characteristic absence of ketosis. Considerable heterogeneity has been observed in clinical and biochemical presentation. Acute episodes of illness have been mistaken for Reye syndrome. The pattern of organic acids in the urine includes large amounts of 3-hydroxy-3-methylglutaric, 3-methyl-glutaconic, 3-methylglutaric and 3-hydroxyisovaleric acids. Smaller, but appreciable levels of glutaric, adipic and other dicarboxylic acids may also be excreted in the urine. Lactic acid may be present in sizable amounts at times of acute illness. The primary defect is a deficiency of 3-hydroxy-3-methylglutaryl-coenzyme A lyase, a key enzyme in the cycle of ketogenesis.

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“…Several specific enzymatic de fects which present as Reye syndrome have been identified including deficiencies of the medium-chain acyl-CoA dehydrogenase (MCAD) [42][43][44][45], hydroxymethylglutarylCoA lyase [46,47], and systemic carnitine deficiency [48,49]. In table I, these enzy matic defects are compared with Reye syn drome.…”

Section: Enzymatic Defects Of Fatty Acid Oxidation Versus Reye Syndromementioning

confidence: 99%