Inherited mitochondrial disease (inborn error of
metabolism) affecting the isoleucine catabolism resulting in recurrent
episodes of ketoacidosis.
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.
Approximately 60 cases have been described.
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.
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.
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.
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.
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.
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.
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 ...