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Severe progressive necrotizing encephalopathy occurring between the age of 3 months and 2 years. Caused by a mitochondrial disorder impeding oxidative phosphorylation. Symptoms include loss of previously acquired motor skills, muscle weakness, hypotonia, lactic acidosis associated with respiratory and kidney dysfunction.

Cytochrome Oxidase Deficiency Disease; Infantile Subacute Necrotizing Encephalopathy; Necrotizing Encephalopathy; Pyruvate Decarboxylase Deficiency; Subacute Necrotizing Encephalomyelitis, X-Linked Infantile Necrotizing Encephalopathy.

Mutation in the oxidative phosphorylation system resulting in necrotizing encephalopathy transmitted either as an autosomal trait or via mitochondrial DNA (maternal transmission only).

Unknown. Male-to-female ratio is 3:2.

Genetic inheritance is variable: about half of cases are autosomal recessive with multiple loci, a few are dominant or X-linked, and the remainder are a result of mitochondrial DNA defects (and thus maternally inherited only).

When related to a mutation in the mitochondrial DNA, a single base pair is changed from thymine to either cytosine or guanidine in the gene coding for ATPase, an enzyme involved in the electron transfer chain allowing oxidative phosphorylation (resulting in deficiency of cytochrome C oxidase, which is the terminal enzyme of the mitochondrial respiratory chain). Because of the vital nature of this process, ATPase is only partially defective in Leigh syndrome, or several types of mitochondria coexist, some with normal ATPase and some with the defective version. Brain neurons are mainly affected, but liver and heart cells also may deteriorate.

Diagnosis is usually made during the first or second year of life with delayed psychomotor development or regression of already acquired skills. Ophthalmoplegia and hypotonia are often associated. Further neurologic signs include poor vision, nystagmus, tremor, ataxia, seizures, positive Babinski sign, and absent tendon reflexes. Respiratory signs include alternation of polypnea “sine materia” and bradypnea, poor response to hypoxia or hypercarbia, and eventually respiratory failure.

Leigh syndrome is a progressive necrotizing encephalopathy, usually presenting with feeding and swallowing problems, dysautonomia, weakness, ataxia, and convulsions. There are several foci of necrosis in the brainstem, putamen, and globus pallidus. Respiratory involvement is late in the evolution and is associated with poor prognosis. Laboratory investigations include elevated lactate and pyruvate levels and low glucose levels in blood and cerebrospinal fluid (CSF). Several enzymes have been involved in Leigh syndrome: a decrease of pyruvate decarboxylase, inhibition of thiamine pyrophosphate-ATP phosphoryl transferase, or blockade of pyruvate dehydrogenase. Pyruvate dehydrogenase is itself a complex of six enzymes. Other mitochondrial genetic defects can lead to the clinical picture of Leigh syndrome. These enzymatic defects prevent entry of pyruvate in the Krebs cycle.

Assess blood lactate and glucose levels. Evaluate breathing pattern. Define a strategy in case of respiratory failure, especially with postoperative management. Check preoperative diet and carbohydrate intake.

Because the brainstem is often involved, meticulous care should be devoted to temperature, airway, and control of ventilation. Prevent hypocarbia because hypocarbia inhibits pyruvate decarboxylase and further increases lactate levels. Prevent hypothermia ...

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