Leigh Syndrome

 Leigh Syndrome (Leigh’s Disease)

Overview

Leigh syndrome (also called Leigh’s disease) is a rare genetic condition that affects your child’s central nervous system. A newborn with Leigh syndrome seems healthy at birth. Over time, cells in their nervous system break down or degenerate. Symptoms, such as feeding problems, seizures and continuous crying, tend to occur when your child is between 3 months and 2 years old.

An inherited gene change (mutation) causes Leigh syndrome. It’s a type of mitochondrial disease. Unfortunately, there isn’t a cure. The condition is fatal, with most children passing away by age 3. In rare instances, the condition develops during adolescence or adulthood.

Mitochondria are your body’s energy factories. These tiny cellular structures convert the energy in fatty acids and glucose into a substance called adenosine triphosphate (ATP). This substance energizes cells.

All cells (except red blood cells) have mitochondria. Mitochondrial diseases occur when mitochondria don’t function as they should. As the energy output of cells diminishes, cell damage or death occurs. Your nervous system requires a lot of energy to function. Leigh syndrome damages or destroys cells in your child’s nervous system that provide energy to their brain, nerves and spinal cord.

Leigh syndrome gets its name from British physician Archibald Denis Leigh, who first described the condition in 1951. He called the condition subacute necrotizing encephalomyelopathy (SNE). Encephalomyelopathy refers to diseases that affect the brain and spinal cord. Today, most healthcare providers use Leigh syndrome or Leigh’s disease when talking about this condition.

Types of Leigh syndrome

The types of Leigh syndrome include:

Early-onset (infantile): The most common form of Leigh syndrome appears before age 2. Providers also call it classical Leigh syndrome or infantile necrotizing encephalopathy. The condition affects boys and girls equally.

Late-onset (adult-onset): Symptoms appear after age 2 and may not occur until adolescence or early adulthood. Adult-onset Leigh syndrome is rare. The condition affects more males than females. The disease progresses slower than the infantile type.

Leigh-like syndrome: A person has some symptoms of Leigh syndrome but imaging scans don’t detect signs of the disease.

Symptoms

Symptoms of Leigh syndrome typically appear within your infant’s first two years of life. At first, your baby may reach expected child development milestones like holding up their head. Then, they start to regress, losing these abilities or showing signs of physical or developmental delays.

Signs of early-onset Leigh syndrome include:

Difficulty swallowing (dysphagia), poor sucking or feeding problems.

Diarrhea and vomiting.

Hypotonia (low muscle tone).

Irritability and chronic crying.

Poor head control and reflexes.

Other symptoms may occur as the disease progresses. These symptoms can also appear with late-onset Leigh’s disease, including:

Dementia.

Movement and balance problems like ataxia.

Dysarthria (difficulty forming words).

Dystonia (involuntary muscle contractions).

Muscle spasms or spasticity.

Partial paralysis.

Peripheral neuropathy

Seizures.

Slowed physical growth.

Causes

Experts have identified mutations in more than 75 different genes that can cause Leigh syndrome. The gene mutations affect your body’s ability to make ATP.

An estimated 8 in 10 children with Leigh syndrome inherit the gene change that causes the condition through one of two ways:

Autosomal recessive disorder: A child inherits the same gene mutation from each parent. The parents are carriers of the changed gene, but they don’t have the disease.

X-linked recessive genetic disorder: A gene change on an X chromosome causes the condition. It can come from the biological mother or father. If one of the mother’s two X chromosomes has the gene change, there’s a 1 in 4 chance that her son or daughter will inherit the mutated gene. If a boy inherits the gene change, they’ll develop Leigh syndrome; a girl will not. However, a daughter can pass the defective gene to her future children. A father can pass a changed X chromosome to his daughter, but not to his son.

Complications of Leigh syndrome

Leigh syndrome can lead to a buildup of lactic acid in your child’s bloodstream, causing lactic acidosis. Your body makes lactic acid when oxygen levels in cells get too low to aid metabolism (the breakdown of carbohydrates into energy). There may also be too much carbon dioxide in their blood.

Lactic acidosis and increased levels of carbon dioxide can lead to:

Breathing problems like shortness of breath (dyspnea), apnea (pauses in breathing) and abnormal or rapid breathing (hyperventilation).

Heart problems like hypertrophic cardiomyopathy (thickened heart muscle).

Kidney problems.

Diagnosis

Your healthcare provider may order:

Blood tests to check for lactic acidosis and enzyme markers that indicate Leigh syndrome.

Imaging scans like an MRI to check for damaged areas of brain tissue (lesions).

Genetic test (a type of blood test) to determine the type of gene change causing the condition.

Treatment

here isn’t a cure for Leigh syndrome. Treatments focus on easing symptoms to keep your child comfortable. Unfortunately, the condition is fatal.

Your child may benefit from:

Citric acid (sodium citrate) or sodium bicarbonate to treat lactic acidosis.

Thiamine (vitamin B1) injections to slow disease progression.

Children with certain enzyme deficiencies may benefit from a high-fat, low-carbohydrate diet. Some children who struggle to eat may need tube feeding (enteral nutrition).

Type of Doctor Department :Primary care physician, Neurologist, Cardiologist, and Eye specialist.