Does your baby have these symptoms? Let's talk about Leigh Syndrome!

It's so exciting to see a newborn baby, isn't it? But sometimes, even if they seem healthy at first, they can start to show strange symptoms after a few months. If they have trouble breastfeeding, cry a lot, or have seizures, these could be signs of a rare genetic condition called Leigh Syndrome. This is really heartbreaking, but it's important to be aware of it.

What is Leigh Syndrome? Simply put...

Leigh Syndrome, also known as Leigh's Disease, is a very rare genetic condition. It mainly affects your baby's central nervous system. That is, the brain, spinal cord, and nerves. Imagine, a baby with this condition appears healthy most of the time when he is born. But over time, the cells in his nervous system gradually weaken or even die.

These symptoms usually begin when the baby is about 3 months old, or before the age of 2. The first things you'll notice are difficulty sucking, refusing to eat, crying for no reason, and seizures.

Unfortunately, there is no permanent cure for Lee syndrome. It is a life-threatening condition. Most children with this condition die before the age of 3. However, very rarely, the condition can occur in young or older adults.

What are Mitochondrial Diseases? The energy factories of our bodies!

To understand this, we first need to know a little about mitochondria . Simply put, mitochondria are like tiny energy factories inside the cells of our bodies. These are the ones that produce energy from the fatty acids and glucose in the food we eat and convert it into a substance called adenosine triphosphate (ATP) . This ATP is what gives our cells the energy to work.

Mitochondria are found in every cell except our red blood cells. Mitochondrial diseases are conditions that occur when these mitochondria do not function properly. The cells do not get the energy they need, which causes the cells to become damaged or die.

Our nervous system needs a lot of energy to function. In Lee syndrome, the cells in a child's nervous system, especially the cells that provide energy to the brain, nerves, and spinal cord, are damaged or destroyed.

Are there other names for Leigh Syndrome?

Yes, this disease was first named by Archibald Denis Leigh, a British physician who described it in 1951. He called it Subacute Necrotizing Encephalomyelopathy (SNE) . Encephalomyelopathy is a disease that affects the brain and spinal cord. However, today, many doctors call it Leigh syndrome or Leigh disease.

What are the main types of Leigh Syndrome?

There are several main types of Lee syndrome:

• Infantile Leigh Syndrome: This is the most common type. Symptoms appear before the child is 2 years old. This is also called Classical Leigh Syndrome. It affects both males and females equally.
• Adult-onset Lee syndrome: Symptoms appear after age 2, sometimes in adolescence or early adulthood. This is very rare. This type affects males more often. Also, the disease progresses more slowly than the early-onset type.
• Leigh-like syndrome: In this case, a person may show some of the symptoms of Leigh syndrome, but imaging scans do not show signs of the disease in the brain.

How common is this disease?

Classical (early) Lee syndrome is estimated to occur in about one in 40,000 newborns worldwide. However, it is more common in some geographic areas. For example:

• One in 2,000 newborns in the Lac-Saint-Jean region of Quebec, Canada.
• One in 1,700 newborns in the Faroe Islands, located between Iceland and Scotland.

The exact reason for this has not been found.

What causes Leigh Syndrome?

Experts have found that Lee syndrome can be caused by mutations in more than 75 genes . These mutations affect our body's ability to produce ATP (energy).

Eight out of 10 children with Lee syndrome inherit the condition in two main ways:

1. Autosomal recessive disorder: In this, the child inherits the same gene mutation from both parents. The parents are only carriers of this mutation and do not have the disease.

2. X-linked recessive genetic disorder: This is caused by a mutation on the X chromosome. It can come from either the mother or the father. If a mother has this mutation on one of her X chromosomes, there is a 1 in 4 chance that either her son or daughter will inherit the mutation. If a boy inherits this mutation, he will develop Lee syndrome; a girl will not. However, the daughter can pass the defective gene on to her future children. A father can pass on a mutated X chromosome to his daughter, but not to his son.

How do changes in mitochondrial DNA cause Lee syndrome?

About 2 in 10 children inherit a mutation in their mitochondrial DNA (mtDNA) from their mother. This mutation can be passed down through generations of a family. Rarely, a spontaneous mtDNA mutation can occur. The most common mtDNA mutation seen in Leigh syndrome is a mutation in the gene MT-ATP6 that prevents the production of ATP.

What are the symptoms of Leigh Syndrome?

Symptoms of Lee syndrome usually appear within the first two years of a baby's life. At first, your baby may reach normal developmental milestones, such as holding their head up straight. Then, they gradually regress, meaning they lose these abilities or show physical or developmental delays.

Early symptoms of Lee syndrome include:

• Difficulty swallowing ( dysphagia ), poor sucking or eating problems.
• Diarrhea and vomiting.
• Lack of muscle tone ( hypotonia ).
• Frequent restlessness and constant crying.
• Weaknesses in head control and reflexes.

As the disease progresses, other symptoms may appear. These symptoms can also be seen in later stages of Lee syndrome. They include:

• A condition like dementia .
• Movement and balance problems, for example ataxia (stumbling while walking, loss of balance).
• Difficulty pronouncing words correctly ( dysarthria ).
• Involuntary muscle contractions ( dystonia ).
• Muscle twitching or stiffness ( spasticity ).
• Partial paralysis.
• Nerve weakness in the limbs ( peripheral neuropathy ).
• Convulsions.
• Slowing of physical growth.

How does Leigh Syndrome affect vision?

Lee syndrome can also affect the nerves in the eyes, causing problems such as:

• Crossed eyes ( strabismus ).
• Optic atrophy ( optic nerve atrophy ).
• Weakness or paralysis of the eyes.
• Involuntary rapid eye movements ( nystagmus ).
• Loss of vision.

In later stages, young people or adults with Lee syndrome may develop color blindness and loss of central vision ( low vision ).

What are the possible complications of Leigh Syndrome?

Lee syndrome can cause a build-up of lactic acid in a child's blood, causing a condition called lactic acidosis . Our bodies produce lactic acid when the oxygen levels in our cells are too low to support metabolism (the conversion of carbohydrates into energy). They may also have an increase in carbon dioxide in their blood.

Lactic acidosis and increased carbon dioxide levels can cause the following:

• Breathing difficulties: shortness of breath ( dyspnea ), temporary cessation of breathing ( apnea ), and abnormal or rapid breathing ( hyperventilation ).
• Heart disease: thickening of the heart muscle ( hypertrophic cardiomyopathy ).
• Kidney problems.

How is Leigh Syndrome diagnosed?

Your doctor may order tests like these:

• Blood tests: Check for enzyme markers that indicate lactic acidosis and Leigh syndrome.
• Imaging tests such as MRI (Magnetic Resonance Imaging) scans: Check for damage to brain tissue (lesions).
• Genetic tests: To find out exactly which genetic mutation is causing the disease.

How is Leigh Syndrome treated?

Unfortunately, there is no permanent cure for Lee syndrome. Treatment is mainly aimed at controlling the symptoms and providing comfort to the child. This is a fatal disease.

Your child may find some relief from things like:

• Treat lactic acidosis with citric acid (sodium citrate) or sodium bicarbonate .
• Giving injections of thiamine (Vitamin B1) to slow down the progression of the disease.

Some children with enzyme deficiencies may benefit from a high-fat, low-carbohydrate diet. Some children who have difficulty eating may need to be fed through a tube (`enteral nutrition`).

What can you do if your child has Leigh Syndrome?

Caring for a child with a life-limiting illness can be challenging. Here are some things you can do to help reduce the stress, anxiety, and depression you may feel during this time:

• Find healthy ways to reduce stress: like talking to a friend or engaging in a hobby you enjoy.
• Join a support group: This can be an in-person or online group. Talking to other parents can help you feel less alone.
• Be well informed about your child's condition, their unique symptoms, and the progression of the disease.
• Make time for yourself. You can only take good care of your child if you are well.
• Get the support services your child needs: such as home healthcare and rehabilitation services.
• Talk to a mental health professional . This is a very difficult time, so don't hesitate to ask for help.

What is the future of someone with Leigh Syndrome?

Most children with Lee syndrome die of respiratory failure by the age of 3. It is very rare for a child with early-onset Lee syndrome to survive into adulthood. People who develop Lee syndrome in adulthood can live into their 50s.

Can Leigh Syndrome be prevented?

If you have a child with Lee syndrome, you can get a genetic test to find out if you or your partner have the gene mutation that causes it. You may decide to meet with a genetic counselor to discuss ways to reduce the risk of future children inheriting the mutation.

When should you see a doctor?

If your child has any of these symptoms, see a doctor immediately:

• Developmental delays or loss of previously existing abilities.
• Difficulty breathing, eating, or swallowing.
• Convulsions.
• Slowing of physical growth.

What should I ask my doctor?

You can ask your doctor questions like these:

• What causes my child to develop Lee syndrome?
• What treatments can help my child?
• What can I do to help my child at home?
• Should my partner and I get genetic testing?
• Should I be aware of signs of complications?

Finally, things to remember (Take-Home Message)

It's normal to feel overwhelmed and sad when you learn that your child has such a rare, life-threatening condition . But remember that you are not alone. It is important to seek treatment from doctors who have expertise in this condition. Because Lee syndrome can affect many different parts of your child's body, including the brain, eyes, heart, and kidneys, you may need to see several different specialists.

These doctors can help you manage your symptoms and connect you with the support services you and your baby need. Then you can enjoy your time with your baby as much as possible. This journey is difficult, but with love, support, and the right medical advice, you will have the strength to face this challenge.

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