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Inherited mitochondrial disease (inborn error of metabolism) affecting the isoleucine catabolism resulting in recurrent episodes of ketoacidosis.

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Beta-Ketothiolase Deficiency (note that beta-ketothiolase describes a group of enzymes, and patients with defects of different thiolases are known to have a different clinical picture); T2 Deficiency; Alpha-Methyl-Acetoacetic Aciduria; Methionine S-Adenosyltransferase (MAT) Deficiency; 2-Alpha Methyl-3-Hydroxybutyricacidemia; 3-Alpha-Oxothiolase Deficiency; 3-Alpha Ketothiolase Deficiency; 3-Alpha KTD Deficiency.

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Approximately 60 cases have been described.

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Inherited in an autosomal recessive mode. The responsible acetoacetyl-CoA thiolase (ACAT) gene has been mapped to chromosome 11q22.3-23.1. The severity of the clinical features and the penetrance within families are variable.

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Mitochondrial ACAT is responsible for cleavage of acetyl-CoA from acetoacetyl-CoA and 2-methylacetoacetyl-CoA, which is an intermediate in the isoleucine metabolism, but also for acetoacetyl-CoA formation in ketogenesis and acetoacetyl-CoA cleavage in ketolysis.

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Based on recurrent episodes of severe ketosis and acidosis without chronic ketosis. Urine analysis before and after an isoleucine challenge (showing 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, butanone, and tiglylglycine) is helpful for diagnosis. Demonstration of the enzyme defect in fibroblasts or leukocytes confirms the definite diagnosis.

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Children with this defect commonly present with failure to thrive, recurrent episodes of severe ketoacidosis with hyperventilation (caused by metabolic acidosis), vomiting, diarrhea (often bloody), and coma during the course of intercurrent infections or after excessive protein intake. Onset is rarely before age 4 months. Most patients (approximately 60%) can have normal mental development if severe metabolic decompensations can be prevented. However, ataxia and frequent headaches have been reported. One case with congestive cardiomyopathy has been described. Mainstay of therapy is moderate restriction of isoleucine intake, intravenous glucose, and sodium bicarbonate during decompensations and avoidance of fasting.

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Most importantly, hypoglycemia during preoperative fasting must be prevented. A dextrose-containing intravenous solution should be started before the preoperative fasting period and kept intraoperatively and postoperatively until regular oral feeds are tolerated again. Cardiomyopathy has been described, so cardiac assessment of the patient is recommended.

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Regional anesthesia allows better monitoring of central nervous function. Lactated Ringer solution should be avoided in patients with mitochondrial diseases because these patients may already have increased lactate levels and acidosis. Glucose and lactate levels in the plasma, as well as ketone levels in the urine, should be monitored perioperatively. Prevent hypothermia, shivering, or other conditions that cause increased energy expenditure.

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No specific literature on anesthesia in patients with ACAT deficiency. Although not all of the various mitochondrial disorders can be summarized and unified, adverse anesthetic experiences in a particular mitochondrial disease should be considered for every patient with mitochondrial dysfunction until further information for specific metabolic defects is available. Most reports refer to anesthesia in patients with mitochondrial myopathy. Muscular sensitivity to muscle-relaxing agents might be enhanced in these patients, and malignant hyperthermia after succinylcholine has been reported on rare occasions. Therefore, although scientific evidence is lacking, it has been advocated that ...

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