Leigh Syndrome

At a glance

It is a severe progressive mitochondrial disorder impeding oxidative phosphorylation with leads to necrotizing encephalopathy between the age of 3 months and 2 years. It has also been reported that the onset begins later during childhood. It causes brain, spinal cord, and optic nerves degeneration and clinically is characterized by acquired motor skills, muscle weakness and hypotonia, lactic acidosis associated with respiratory and kidney dysfunctions. The association with hypertrophic cardiomyopathy has been reported and represents a major anesthesia consideration. Although malignant hyperthermia (MH) has not been reported with Leigh disease, it may be wise to avoid triggering agents as other myopathic conditions with a propensity for MH have been misdiagnosed in the past in the presence of muscular disorders.

Synonyms

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

History

It is named after Archibald Denis Leigh, a British neuropsychiatrist, who first described the condition in 1951.

Nature

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

Classification

There are three types of Leigh disease described which consists of the following:

1. Infantile Necrotizing Encephalopathy (Classical Form): Clinically associated with a rapidly progressive neurological degenerative disorder that begins between the ages of 3 months and 2 years. Previously acquired motor skills, such as loss of head control and poor sucking, begins at the age of 3 months and is considered pathognomonic of the disease. Other features include profound loss of appetite, recurrent vomiting, irritability, continuous crying, and possible seizure activity.

2. X-Linked Infantile Necrotizing Encephalopathy: Clinical condition similar to the classical Leigh Syndrome except that it is predominant in males.

3. Adult-Onset Subacute Necrotizing Encephalomyelopathy: Very rare progressive form presenting clinically during adolescence or early adulthood. It is characterized by central scotoma, color blindness, and bilateral optic atrophy. The manifestation of ataxia appears around the age of 50. Other late features include partial paralysis, spastic paresis, clonic muscle jerks, grand mal seizures, and/or dementia.

Incidence

Although the exact incidence remains unknown, the prevalence is often estimated in the literature at 1:36,000 to 40,000 live births. The classical form develops during infancy (infantile necrotizing encephalopathy) usually between the ages of 3 months and 2 years. It affects males and females equally. Patients affected with an X-linked recessive trait typically present the disease during infancy and males are affected twice as often than females.

Genetic inheritance

The genetic inheritance is described as variable. In most cases, it is presumed inherited as an autosomal recessive trait with multiple loci. There are few autosomal dominant or X-linked ...