About Leigh Syndrome

Leigh Syndrome

Leigh syndrome is a progressive neurometabolic disorder that can cause deterioration of the central nervous system, including the brain, spinal cord, and optic nerve.  It has a general onset in infancy or childhood, often after a viral infection, but can also occur in teens and adults. It is characterized on magnetic resonance imaging (MRI) by visible necrotizing (dead or dying tissue) lesions on the brain, particularly in the midbrain and brainstem. The prognosis for Leigh syndrome is poor. Depending on the defect, individuals typically live anywhere from a few years to the mid-teens. Those diagnosed with Leigh-like syndrome or who do not display symptoms until adulthood tend to live longer.

Long Name: Subacute Necrotizing Encephalomyelopathy

Symptoms: Seizures, hypotonia, fatigue, nystagmus, poor reflexes, eating and swallowing difficulties, breathing problems, poor motor function, ataxia

Causes: Pyruvate Dehydrogenase Deficiency, Complex I Deficiency, Complex II Deficiency,Complex IV/COX Deficiency, NARP

The child often appears normal at birth but typically begins displaying symptoms within a few months to two years of age, although the timing may be much earlier or later. Initial symptoms can include the loss of basic skills such as sucking, head control, walking and talking. These may be accompanied by other problems such as irritability, loss of appetite, vomiting and seizures. There may be periods of sharp decline or temporary restoration of some functions. Eventually, the child may also have heart, kidney, vision, and breathing complications.

There is more than one defect that causes Leigh syndrome. According to Dr. David Thorburn, at least 26 defects have been identified. These include a pyruvate dehydrogenase (PDHC) deficiency, and respiratory chain enzyme defects – Complexes I, II, IV, and V. Depending on the defect, the mode of inheritance may be X-linked dominant (defect on the Xchromosome and disease usually occurs in males only), autosomal recessive (inherited from genes from both mother and father), and maternal (from mother only). There may also be spontaneous cases which are not inherited at all.

One estimate of the incidence of Leigh syndrome (Leigh syndrome: Clinical Features and Biochemical and DNA Abnormalities by Dr. David Thorburn, PhD of Melbourne, Australia) is one in 77,000 births or one per 40,000 births for Leigh and Leigh-like disease (a milder version of the syndrome, often not proven by imaging or autopsy). However, this may be an underestimate since mitochondrial diseases tend to be under-diagnosed and misdiagnosed.

There is no cure for Leigh syndrome. Treatments generally involve variations of vitamin and supplement therapies, often in a “cocktail” combination, and are only partially effective. Various resource sites include the possible use of: thiamine, coenzyme Q10, riboflavin, biotin, creatine, succinate, and idebenone. Experimental drugs such as dichloroacetate (DCA) are also being tried in some clinics. In some cases, a special diet maybe ordered and must be monitored by a dietitian knowledgeable in metabolic disorders.

Currently, there is a clinical drug trial underway for Leigh syndrome – EPI-743.

Mitochondrial Disease

Mitochondrial diseases result from failures of the mitochondria, specialized compartments present in every cell of the body except red blood cells.

Mitochondria are responsible for creating more than 90% of the energy needed by the body to sustain life and support growth. When they fail, less and less energy is generated within the cell. Cell injury and even cell death follow. If this process is repeated throughout the body, whole systems begin to fail, and the life of the person in whom this is happening is severely compromised. The disease primarily affects children, but adult onset is becoming more and more common.

Diseases of the mitochondria appear to cause the most damage to cells of the brain, heart, liver, skeletal muscles, kidney and the endocrine and respiratory systems.

Depending on which cells are affected, symptoms may include loss of motor control, muscle weakness and pain, gastro-intestinal disorders and swallowing difficulties, poor growth, cardiac disease, liver disease, diabetes, respiratory complications, seizures, visual/hearing problems, lactic acidosis, developmental delays and susceptibility to infection.

*Courtesy of the United Mitochondrial Disease Foundation