About Leigh Syndrome
Mitochondria turn food and oxygen into the energy every cell runs on, and the brain uses more of it than any other organ. In Leigh syndrome a genetic fault in one of the energy-making steps, most often complex I or complex IV of the respiratory chain, or the pyruvate dehydrogenase enzyme, leaves nerve cells in the basal ganglia and brainstem starved of energy. Those regions control movement, swallowing, eye movement and breathing, which is why the disease looks the way it does. On a brain MRI the damage shows up as matching bright spots on both sides of those structures, and lactate is often raised in the blood or spinal fluid, especially during an illness.
The course is usually stepwise rather than steady. A child does well for a stretch, then an infection or fever triggers a sudden decline, followed by partial recovery to a new, lower baseline. Most children have at least one of these sudden declines, which may require hospitalization, and up to half die before age 3, most often from breathing or heart failure. Some children have stable periods lasting years, and outcomes vary widely: very early onset, brainstem involvement, the MT-ATP6 m.8993T>G change and MT-ND5 changes have been linked to more severe disease, published reports on SURF1 conflict, and a small number of subtypes, such as the thiamine transporter gene SLC19A3, respond to high-dose vitamins if caught early.
Diagnosis today rests on genetic testing, usually a nuclear gene panel or whole-exome sequencing plus mitochondrial DNA sequencing that measures the mutant load, rather than the muscle biopsy or autopsy that defined the disease for decades. Care is supportive: nutrition (often by feeding tube), seizure control, avoiding the drug valproate and other metabolic stressors, and a vitamin and cofactor mix that many specialists prescribe despite limited trial evidence.
Common Symptoms of Leigh Syndrome
Recognizing the signs of Leigh Syndrome early can lead to faster diagnosis and better outcomes. Symptoms may vary in severity from person to person. If you or a loved one are experiencing any of the following, consider speaking with a specialist.
- Vomiting, diarrhea, trouble swallowing and poor weight gain, often the first signs
- Loss of skills a child had already learned, with floppy muscle tone
- Stiff or twisting postures (dystonia), unsteady balance and tremor
- Irregular breathing, with pauses or unusually fast or slow breaths, from damage to the brainstem
- Weak eye muscles, jerky eye movements and vision loss from optic nerve damage
- Seizures, and in some children a thickened heart muscle, hearing loss, or liver or kidney problems
Who Leigh Syndrome Affects
Symptoms usually begin in the first year of life, often appearing or sharply worsening during a fever or infection. More than 130 genes can cause it (over 120 in the nuclear DNA and 15 in the mitochondrial DNA): about 70% to 80% of cases come from nuclear genes, usually inherited from both parents (autosomal recessive, a 1 in 4 chance in each pregnancy), and roughly 20% to 30% from mitochondrial DNA, which is inherited only through the mother, though some changes arise new in the child. In mitochondrial DNA cases, the share of mutated copies (heteroplasmy) can influence severity, most clearly for the MT-ATP6 m.8993 changes. A few genes, such as PDHA1, are X-linked. A minority of people first develop symptoms as teenagers or adults, with ataxia, nerve damage or psychiatric symptoms.
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Trusted Leigh Syndrome Resources
Reputable organizations and medical references for learning more about Leigh Syndrome, including disease registries, foundation resources, and clinical guidelines.