Infantile neuroaxonal dystrophy: Year of the Zebra

Infantile neuroaxonal dystrophy, or INAD for short, is a rare and rapidly progressive neurodegenerative disorder that begins in early childhood. 

It is caused by mutations affecting the PLA2G6 gene, which provides instructions for making an enzyme called phospholipase A2. This enzyme is important for breaking down fatty molecules called phospholipids, which are one of the main components of the cell membrane. Impaired function of phospholipase A2 is thought to disrupt the structure of the cell membrane, resulting in the degeneration of nerve cells. 

INAD is typically inherited in an autosomal recessive pattern, meaning two copies of the mutated gene must be present for individuals to develop the disorder. 

Alright, now clinical manifestations of INAD typically begin between six  months and three years of age. 

Initially, children with INAD can meet their developmental milestones but then begin to experience delays in reaching milestones like crawling or talking. As the disorder progresses, children experience a regression in motor, verbal, and cognitive skills. For example, a child who could initially speak a few words or grasp objects with their hand will gradually lose these skills. Of note, individuals with INAD commonly experience progressive dementia by three years of age.

Individuals with INAD may also have visual problems like strabismus, where the eyes do not align with each other; nystagmus, which is the presence of involuntary, rapid eye movements; and some may even develop vision loss.