Neuroaxonal dystrophy, late infantile

Neuroaxonal Dystrophy, Late Infantile

Neuroaxonal dystrophy, late infantile, is a rare neurodegenerative disorder characterized by the progressive degeneration of axons, the long threadlike part of a nerve cell along which impulses are conducted from the cell body to other cells. This condition typically presents in early childhood and is part of a group of disorders known as neurodegeneration with brain iron accumulation (NBIA).

Clinical Presentation

Children with late infantile neuroaxonal dystrophy (LINAD) usually begin to show symptoms between the ages of 2 and 6 years. The clinical features include:

• Developmental regression: Loss of previously acquired motor and cognitive skills.
• Hypotonia: Decreased muscle tone, leading to floppy limbs.
• Ataxia: Lack of voluntary coordination of muscle movements.
• Dystonia: Sustained or repetitive muscle contractions resulting in twisting and repetitive movements or abnormal fixed postures.
• Optic atrophy: Degeneration of the optic nerve, leading to vision loss.
• Seizures: Occurrence of convulsions or fits.

Pathophysiology

The pathophysiology of neuroaxonal dystrophy involves the accumulation of abnormal deposits in the axons of neurons. These deposits are known as spheroid bodies and are composed of disorganized neurofilaments and other cellular debris. The exact cause of these deposits is not fully understood, but they lead to the disruption of normal neuronal function and eventual cell death.

Genetic Basis

Neuroaxonal dystrophy, late infantile, is often associated with mutations in the PLA2G6 gene, which encodes an enzyme called phospholipase A2 group VI. This enzyme is involved in the metabolism of phospholipids, which are essential components of cell membranes. Mutations in this gene disrupt normal phospholipid metabolism, leading to the accumulation of spheroid bodies in neurons.

Diagnosis

Diagnosis of LINAD is based on clinical evaluation, neuroimaging, and genetic testing.

• MRI: Magnetic resonance imaging of the brain typically shows iron accumulation in the basal ganglia and cerebellar atrophy.
• Genetic testing: Identification of mutations in the PLA2G6 gene confirms the diagnosis.

Management

There is currently no cure for neuroaxonal dystrophy, late infantile. Management is supportive and focuses on alleviating symptoms and improving quality of life. This may include:

• Physical therapy: To maintain mobility and prevent contractures.
• Occupational therapy: To assist with daily living activities.
• Medications: To manage symptoms such as seizures and muscle stiffness.

Prognosis

The prognosis for children with LINAD is poor, with progressive neurological decline leading to severe disability and early death, often in the second decade of life.

Also see

• Neurodegeneration with brain iron accumulation
• PLA2G6-associated neurodegeneration
• Infantile neuroaxonal dystrophy
• Dystonia
• Optic atrophy