Understanding INAD

Infantile Neuroaxonal Dystrophy (INAD) is a rare, autosomal recessive, neurodegenerative disorder that affects young children, causing a progressive loss of motor and cognitive skills. It is classified under Neurodegeneration with Brain Iron Accumulation (NBIA) disorders and is also considered a subset of PLAN (phospholipase-associated neurodegeneration). INAD is associated with disruptions in phospholipid remodeling and disruptions in recycling fatty acids, which contribute to the formation of spheroid bodies in nerve endings, ultimately leading to progressive neurodegeneration.

About INAD

Gain a foundational understanding of Infantile Neuroaxonal Dystrophy (INAD), including how common it is, its global impact, and what causes this devastating condition.

Prevalence

Globally, around 4,500 individuals have been diagnosed with INAD, suggesting that it affects roughly 1 in every 1 million people.

Global Impact and Challenges in Diagnosis

Due to its rarity, INAD is often misdiagnosed or underreported, making it challenging to determine its true prevalence. However, advances in genetic testing have improved diagnostic accuracy, resulting in a slight increase in identified cases in recent years.

Cases of INAD have been identified across diverse populations worldwide. Recent large-scale epidemiological studies suggest the highest prevalence to be in Africa and East Asia.

Cause of INAD

• The PLA2G6 mutation leads to defective or absent PLA2 Group6 enzyme activity, disrupting the normal breakdown and recycling of lipids in nerve cells.

• This results in the accumulation of abnormal substances, leading to progressive nerve damage, brain atrophy, and iron buildup in the basal ganglia (a hallmark of some cases).

Medical Aspects & Diagnosis

Learn about the clinical signs of INAD, how it is diagnosed, and the genetic factors that contribute to its development. Early recognition is key to guiding care and support.

Symptoms & Signs

Symptoms typically appear between 6 months and 2 years and progressively worsen. Signs may include:

Developmental regression – Loss of previously acquired skills

Motor difficulties – Trouble walking, muscle weakness, loss of coordination

Vision impairment – Strabismus (crossed eyes) & nystagmus (involuntary eye movements) are often one of the very first indications of INAD, followed by optic atrophy (deterioration of the nerve that connects the eye to the brain).

Overactive reflexes is seen at the beginning of the disease and the absence of reflexes is seen later as the disease progresses. Due to an impairment of the function of cranial nerves (Bulbar dysfunction), children affected by INAD often have speech problems, difficulty speaking, slurred or weak voice

Nutritional problems such as Dysphagia (difficulty swallowing), difficulty chewing, choking on liquids and nasal regurgitation. Due to these challenges of eating and drinking, children are often put on feeding tubes. Some children experience seizures in early stages, some may experience seizures as the disease progresses

Diagnosis & Testing

A combination of medical tests helps diagnose INAD: Diagnosing Infantile Neuroaxonal Dystrophy (INAD) typically involves a combination of clinical evaluation, genetic testing, and imaging studies. The key diagnostic methods include:

1. Clinical Assessment – A neurologist evaluates developmental milestones, motor function, and signs of neurodegeneration, such as muscle weakness, spasticity, and loss of previously acquired skills.

2. Genetic Testing – A definitive diagnosis is usually confirmed through genetic testing, which identifies mutations in the PLA2G6 gene, the primary gene associated with INAD.

This can be done via: • Whole Exome Sequencing (WES) • Targeted PLA2G6 gene sequencing • Whole Genome Sequencing (WGS)

3. Brain MRI – Imaging may show characteristic features of INAD, such as: • Cerebellar atrophy (shrinkage of the cerebellum) • Abnormalities in the basal ganglia • White matter changes

4. Electrophysiological Tests – Tests like nerve conduction studies or electroencephalography (EEG) may be used to assess nerve and brain function, though they are not specific for INAD.

5. Biopsy (Less Common) – A skin or nerve biopsy may sometimes be used to detect spheroid bodies (abnormal nerve endings), but genetic testing has largely replaced this method.

Since INAD symptoms can resemble other neurodegenerative disorders, a combination of these diagnostic tools helps ensure an accurate diagnosis.

Genetic Inheritance

INAD follows an autosomal recessive inheritance pattern, meaning a child must inherit two mutated copies of the PLA2G6 gene—one from each parent—to develop the condition.

• Parents who each carry one mutated copy of the gene are carriers but do not show symptoms.

• When both parents are carriers, each pregnancy has a 25% chance of the child having INAD, a 50% chance of being a carrier, and a 25% chance of inheriting two normal copies of the gene.

Disease Progression & Treatment

Explore how INAD progresses over time, life expectancy for those affected, and current efforts to find effective treatments or a potential cure.

Progression & Life Expectancy

Progression of INAD:

• Onset (6 months – 3 years): Early signs include developmental delays, loss of previously acquired skills (especially motor skills), muscle weakness, and difficulty with coordination.

• Early to Mid-Stage (Toddlerhood – Early Childhood): Rapid progression with worsening muscle tone (spasticity), loss of head control as well as the ability to sit, crawl or walk, regression in speech, and difficulty swallowing. Vision problems, including optic atrophy, may also develop.

• Later Stages (Childhood – Adolescence): Severe muscle weakness, spasticity, and joint contractures lead to loss of voluntary movement. Most children become fully dependent on caregivers. Seizures and respiratory complications become common.

Life Expectancy: The life expectancy for children with INAD varies but is typically between 8 to 12 years, with some children living into their teenage years. The leading causes of death are often respiratory infections or complications related to immobility. There is currently no cure for INAD, but supportive care (such as physical therapy, feeding support, and respiratory care) can improve quality of life.

Is There a Cure for INAD?

Currently, there is no cure for INAD, but research into gene therapy, targeted drugs, and neuroprotective treatments offers hope.

Click here for more information regarding Therapeutic Strategies supported by the INADcure Foundation

Care & Management

Learn about the clinical signs of INAD, how it is diagnosed, and the genetic factors that contribute to its development. Early recognition is key to guiding care and support.

How to Care for a Loved One with INAD

Care focuses on symptom management, including:
✅ Physical & Occupational Therapy – Supports mobility and comfort
✅ Seizure & Spasticity Management – Medications to ease symptoms
✅ Nutritional Support – Feeding tubes to ensure adequate nutrition
✅ Assistive Devices – Wheelchairs and adaptive equipment

Symptom Management

Since INAD has no cure, treatment focuses on managing symptoms and improving the child’s comfort and quality of life. Here are some key areas of care:

1. Physical and Occupational Therapy
• Helps maintain joint flexibility and reduce contractures.
• Stretching exercises can ease muscle stiffness and spasticity.
• Adaptive equipment (such as braces or positioning aids) can provide postural support.

2.Respiratory Care
• Children with INAD are prone to respiratory infections due to weak muscles and swallowing difficulties.
• Chest physiotherapy, suctioning, and nebulizers can help clear mucus.
• A BiPAP or CPAP machine may be needed if breathing difficulties worsen.

3. Nutrition and Feeding Support
• As swallowing becomes difficult, a modified diet or thickened liquids can prevent choking.
• A feeding tube (G-tube) may be needed for safe nutrition and hydration.

4. Seizure Management
• Seizures can be treated with antiepileptic medications.
• A neurologist can help adjust medications as needed.

5.Vision and Hearing Support
• Children may develop optic atrophy, leading to vision loss.
• Regular ophthalmology and audiology evaluations can help track changes and ensure the best possible sensory support.

6. Comfort and Pain Management
• Muscle relaxants (like Baclofen) or Botox injections may help with spasticity.
• Positioning aids, massage therapy, and warm baths can provide comfort.

**Add link to our clinical care guidelines once published

How You Can Help

Your support is crucial in funding research and helping other families affected by INAD.

💙 Donate to accelerate treatment development

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At INADcure Foundation, we are committed to finding treatments, supporting families, and ultimately curing INAD. Together, we can give children with INAD the hope they deserve.

Learn more, get involved, and join the fight against INAD today.