Infantile Neuroaxonal Dystrophy (INAD)

What is infantile neuroaxonal dystrophy (INAD)?

Infantile neuroaxonal dystrophy (INAD) is a rare disease that causes fat substances (lipids) to build up on nerves. It affects nerve signals, leading to a gradual loss of muscle control, vision, speech and intellectual development. These symptoms typically appear in infancy but may occur as late as adolescence.

An inherited gene change (mutation) causes INAD. It’s a type of lipid storage disorder. Unfortunately, there isn’t a cure for this life-threatening condition.

What is a lipid storage disorder?

Lipid storage disorders are a type of inherited metabolic disorder. These disorders affect your metabolism, which helps convert food into energy and rids your body of toxins.

Lipids are fatty substances found in cell membranes and the myelin sheath that protects nerves in your brain and spinal cord. These are critical parts of your nervous system. When you have a lipid storage disorder, your body stores the accumulating lipids. You develop a storage disorder.

Lipid storage disorders like INAD are progressive diseases. The symptoms get worse as lipids continue building up in your body.

What does “infantile neuroaxonal dystrophy” mean?

You may better understand this disease when you break down each word’s meaning:

• Infantile: INAD is present at birth (a congenital disease). Symptoms typically appear during infancy and before a child is 3 years old.
• Neuroaxonal: The disease affects axons in nerve cells. Axons carry messages from your brain to the rest of your body.
• Dystrophy: Dystrophy is the medical term for disorders that cause tissues, organs and muscles to waste away.

What are other names for infantile neuroaxonal dystrophy (INAD)?

Some healthcare providers also use the term “Seitelberger’s disease” to refer to INAD. Dr. Seitelberger first described the disorder in the 1950s. You may also hear the term “PLA2G6-associated neurodegeneration” or PLAN.

What are the types of INAD?

Infantile neuroaxonal dystrophy is the most common type. Healthcare providers may call it the classic form of INAD. As the name implies, symptoms are evident during infancy.

With atypical INAD (aNAD), symptoms appear around age 4, or more rarely, as late as the teen years. Your child may have speech delays or appear to have autism spectrum disorder. The disease progression is slower.

How common is INAD?

INAD is an extremely rare disease. It may affect 1 child out of every 1 million to 2 million children.

What causes infantile neuroaxonal dystrophy (INAD)?

Children with INAD inherit a changed or mutated PLA2G6 gene from each parent. This gene helps make an enzyme (a type of protein) called A2 phospholipase that breaks down fats called phospholipids. This type of fat metabolism keeps nerve cells intact so they function properly.

In children with INAD, the changed PLA2G6 gene hinders enzyme production and function. Sphere-shaped substances called spheroid bodies build up on nerves. These deposits often accumulate on nerve endings that connect to their eyes, muscles and skin. Iron may also build up on their brain.

Who is at risk for INAD?

Infantile neuroaxonal dystrophy is an autosomal recessive disorder. This means a child must inherit a copy of a changed PLA2G6 gene from each parent in order to develop the disease. The child’s parents are carriers of the mutated gene, but they don’t have the disease.

When both parents have the mutated gene, each of their children has a:

• 1 in 4 chance of not getting the mutated gene (no risk of disease).
• 1 in 4 chance of developing INAD.
• 1 in 2 chance of being a carrier who doesn’t develop INAD disease.

What are the symptoms of INAD?

With classic INAD, your infant is often on track for normal child development for the first six months to three years of life. Then, they slowly begin to lose acquired skills like sitting, crawling, walking and talking. This regression is often due to muscle wasting, which leads to low muscle tone (hypotonia). Your child may appear floppy, especially in their trunk area. As the disease progresses, muscle stiffness or spasticity occurs.

Children with INAD may also experience:

• Ataxia (coordination and balance problems).
• Difficulty swallowing (dysphagia).
• Hearing loss.
• Inability to hold up or control their heads.
• Loss of cognitive function that leads to dementia.
• Seizures.
• Speech problems (dysarthria) due to muscle weakness.
• Squinting, wobbly eye movements (nystagmus) or other problems like loss of vision.

Infants with INAD often have distinct facial changes noticeable at birth, such as:

• Crossed eyes (strabismus).
• Large, low-setting ears.
• Prominent forehead.
• Small nose or jaw.

How is INAD diagnosed?

If this disease runs in your family, a prenatal test can determine whether your unborn baby has inherited the mutated gene. A chorionic villus sampling (CVS) test checks placenta cells for the genetic mutation.

Tests for infants, children and adults include:

• Blood test to look for the mutated PLA2G6 gene. A genetic test identifies the disease in 8 of 10 children with INAD.
• Electroencephalogram (EEG) to look for seizure activity.
• MRI to look for changes to the brain.
• Nerve conduction test like an electromyogram.
• Skin biopsy or a biopsy on nerves or tissue to look for spheroid bodies in nerve axons.

How is infantile neuroaxonal dystrophy (INAD) treated?

There isn’t a medical treatment or cure for infantile neuroaxonal dystrophy. Treatments focus on easing symptoms to keep your child comfortable. These therapies include:

• Anticonvulsants (seizure medications).
• Feeding tube (enteral nutrition).
• Medications to ease stiff muscles.
• Pain relievers.
• Physical therapy and proper positioning to support a child’s head and weakened muscles.
• Sedatives.

What new treatments for INAD are in development?

Medical experts are conducting research and clinical trials to find new ways to stop the disease progression and potentially cure INAD. Potential therapies in development include:

• Enzyme replacement therapy.
• Gene therapy.

Can you prevent INAD?

If you and your partner carry the mutated gene that causes INAD, you can meet with a genetic counselor to discuss ways to prevent passing it to your children. One method uses preimplantation genetic diagnosis (PGD) to identify embryos that don’t have the changed gene. Your healthcare provider uses in vitro fertilization (IVF) to implant these embryos into your uterus.

What is the outlook for a child with INAD?

An infant with INAD may appear alert and responsive during their first few years. But as the disease progresses, you’ll notice a regression in vision, speech, motor skills and interactions. The disease can affect breathing, leading to respiratory infections like pneumonia. Most children with INAD die before age 10.

Kids who have the atypical form (aNAD) may start to decline when they’re between 7 and 12 years of age. They live longer than children with INAD, but their life span is still shortened.

Caring for a child with a debilitating condition can take a physical and emotional toll. You may be at risk for depression or other problems. It’s important to ask for support, take time for yourself and enjoy happy moments with your family.

When should I call the doctor?

Call your healthcare provider if your child experiences:

• Balance, movement or gait (walking) problems.
• Breathing problems.
• Muscle weakness or spasms.
• Speech or swallowing difficulties.
• Vision or hearing problems.

What should I ask my provider?

You may want to ask your healthcare provider:

• What type of INAD does my child have?
• What treatments can help?
• What steps can we take at home to ease symptoms?
• What medical specialists should we see?
• Should my family get tested for the gene mutation?
• Should I look for signs of complications?

A note from Cleveland Clinic

Finding out your child has an untreatable disease like infantile neuroaxonal dystrophy (INAD) is life-changing. This lipid storage disorder affects your child’s ability to move, see, eat and talk. While therapies can keep your child comfortable, there isn’t a cure. Although, promising research and clinical trials are underway. If you have the mutated gene that causes INAD, talk to your healthcare provider about ways to lower the chances of passing it to future generations.