Leigh Syndrome: Symptoms & Etiology

Adult-Onset Leigh syndrome
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Leigh syndrome has been noted as effecting infants to early childhood, between the ages of 3-24 months. It effects both sexes equally at 1 in 36,000-40,000 life births (NORD). It is characterized by deterioration of the spinal cord, brain, and optic nerve, which is located in the central nervous system.

Leigh Syndrome Groups

  • Infantile Necrotizing Encephalopathy – better known, as the classic form with onset occurring slowly. The first signs of Leigh is loss of fine and gross motor skills, which includes grasping, reaching, sitting, standing, and walking. When onset appears at the age of 3 months, noticeable loss of the ability to suck and move head will be noted. Loss of appetite, vomiting, and potential seizure activity may occur. Failure to thrive is inevitable at this point.
  • X-Linked Infantile Necrotizing Encephalopathy – is linked to heredity and can occur in utero. An anomaly of the mtDNA (MT-ATP6) may be the culprit, but it has not been fully determined. These anomalies will cause an interruption in the protein complexes (I, II, IV, V) to assemble or a malformed protein, which will interfere with their role in oxidative phosphorylation. Neurons located in the brain stem and basal ganglia will be affected, which will lead to their death. X-Linked traits cannot be passed from father to son. This form of Leigh syndrome only affects males and is recessed from mother and father or mother only.
  • Adult-Onset Subacute Necrotizing Encephalomyelopathy – onset will begin around adolescence with the onset of blurry vision, central scotoma (colorblindness), and leading to blindness. Onset will often occur after being triggered, by a viral infection.

Cytochrome c oxidase (COX) has been linked to 75-80% of Leigh syndrome. Anomalies in the SURF1 gene, which is attached to the chromosome 9. This effects the pyruvate dehydrogenase complex (mitochondrial respiratory complex), which is responsible for transforming pyruvate into acetyl-CoA. This process is called pyruvate decarboxylation. X-linked recessive and mitochondrial inheritances are further modes of transmission of Leigh syndrome.

Symptoms

Children that experience an onset after the age of 24 months will exhibit dysarthria (difficulty articulating words) and ataxia (regulating voluntary movements). These children may have been diagnosed with mental retardation and diminishment in their intellectual skills previous to the onset.

  • Hypotonia (decreased muscle tone)
  • Spasticity (muscle spasms and tremors)
  • Devoid of tendon reflexes
  • Dyspnea (difficulty breathing) with or without apnea (periods of respiratory cessation)
  • Dysphagia (difficulty swallowing)
  • Nystagmus (rapid eye movement) and ophthalmoplegia (eye muscle paralysis)
  • Hypertropic cardiomyopathy (enlargement of the heart)
  • Peripheral neuropathy (CNS disorder)
  • Partial paralysis

Etiology

A deficieny in the mitochondrial respiratory chain enzymes and anomalies of the mitochondria DNA are linked to Leah syndrome. There has not been a genetic factor linked to Leigh, as of yet. Cysts may be noted in the cerebral cortex.

Diagnosis

  • Magnetic Resonance Imaging (necrotic brain tissue, which causes lesions)
  • Computed Tomography
  • Blood Glucose Testing
  • Complete Blood Count
  • Blood Smear
  • Platelet Count
  • Blood and serum thiamin phosphate (may be present in the blood and urine)

Pyruvate dehydrogenase complex and COX enzymes deficiencies  may be noted.

Treatment

  • Thiamine (Vitamin B1) supplements
  • Low Carbohydrate diet (X-linked form)
  • Oral Sodium Bicarbonate
  • DCA (dichloracetate) is an experimental drug that has been tried, in some cases, but outcome is not determined