Leigh Necrotizing Encephalopathy; Leigh's Syndrome; Necrotizing Encephalomyelopathy of Leigh's; SNE; Subacute Necrotizing Encephalopathy; Infantile Subacute Necrotizing Encephalopathy; Juvenile Subacute Necrotizing Encephalopathy; Leigh Syndrome; Leigh Disease; Subacute Necrotizing Encephalomyelopathy

Leigh's disease is a rare inherited neurometabolic disorder that affects the central nervous system. This progressive disorder begins in infants between the ages of three months and two years. Leigh's disease can be caused by mutations in mitochondrial DNA or by deficiencies of an enzyme called pyruvate dehydrogenase. Genetic mutations in mitochondrial DNA interfere with the energy sources that run cells in an area of the brain that plays a role in motor movements. There is also a form of Leigh’s disease called X-linked Leigh’s disease, which is the result of mutations in a gene that produces another group of substances that are important for cell metabolism. This gene is only found on the X chromosome. Symptoms of Leigh's disease usually progress rapidly. The earliest signs may be poor sucking ability, and the loss of head control and motor skills. These symptoms may be accompanied by loss of appetite, vomiting, irritability, continuous crying, and seizures.

Diagnostic testing: Molecular genetic testing can differentiate between mtDNA-associated Leigh syndrome (caused by mutations in mtDNA) and nuclear gene-encoded Leigh syndrome (caused by mutation in nuclear DNA). Leigh syndrome vary greatly and may be diagnosed by:

• •

  Progressive neurologic disease with motor and intellectual developmental delay;

• •

  Signs and symptoms of brainstem and/or basal ganglia disease;

• •

  Raised lactate concentration in blood and/or cerebrospinal fluid (CSF); and

• •

  The presence of one or more of the following:

  • –

    Characteristic features on brain imaging (CT scan or MRI);

  • –

    Typical nervous system tissue changes; or

  • –

    Typical nervous system tissue changes in a similarly affected sibling.

Physical findings: Most individuals with Leigh syndrome have central nervous system and peripheral nervous system abnormalities, without involvement of other body systems.

Central nervous system abnormalities may include:

• •

  Developmental delay or regression;

• •

  Nystagmus;

• •

  Ophthalmoparesis (weakness in the muscles that control eye movement);

• •

  Optic atrophy;

• •

  Ataxia;

• •

  Dysphagia;

• •

  Retinitis pigmentosa; and

• •

  Deafness.

Peripheral nervous system abnormalities may include polyneuropathy and myopathy.

Although most people with Leigh syndrome only have neurological abnormalities, some people also have non-neurologic abnormalities. These may include:

• •

  Distinct physical features;

• •

  Hormone abnormalities resulting in short stature or hypertrichosis;

• •

  Heart abnormalities (hypertrophic or dilated cardiomyopathy); and

• •

  Gastrointestinal symptoms, such as diarrhea.

As the disorder progresses, symptoms may also include:

• •

  Generalized weakness;

• •

  Lack of muscle tone; and

• •

  Episodes of lactic acidosis, which can lead to impairment of respiratory and kidney function.

ICD-9: 330.8

The most common treatment for Leigh's disease is thiamine or Vitamin B1. Oral sodium bicarbonate or sodium citrate may also be prescribed to manage lactic acidosis. Researchers are currently testing dichloroacetate to establish its effectiveness in treating lactic acidosis. In children who have the X-linked form of Leigh’s disease, a high fat, low-carbohydrate diet may be recommended.

The prognosis for children with Leigh's disease is poor. Children who lack mitochrondrial complex IV activity and those with pyruvate dehydrogenase deficiency tend to have the worst prognosis and die within a few years. Those with partial deficiencies have a better prognosis, and may live to be 6 or 7 years of age. Some have survived to their mid-teenage years.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

• •

  Clinical history and examination describing the diagnostic features of the impairment physical findings;

• •

  Family history;

• •

  Muscle biopsy;

• •

  Genetic testing;

• •

  Electromyography or nerve conduction tests; and

• •

  Blood enzyme tests.

Suggested Listings for Evaluation: