Late Infantile onset NCL

Classical infantile NCL is due to a mutation in the CLNI gene which leads to a deficiency and enzyme called  palmitoyl protein thioesterase 1 (PPT1). The lack of adequate amounts of PPT1 leads to the build up of waste products in the cell which somehow leads to cell death. These accumulations of materials can be seen with an electron microscope and are known as granular osmiophilic deposits (GROD).

Age at Onset and First Symptoms

A child with INCL progresses normally and parents do not become worried about the motor and or mental development of their children until the age of 10 to 18 months.  However, the rate of head growth begins to decrease in several children as early as 5 months, indicating that the symptoms become apparent several months after the onset of the disease. Hyper excitability or being unsettled, including sleep problems, muscular hypotonia or floppiness and lack of normal development in the fine motor skills are additional early signs. In the majority of children with INCL, the normal development begins to slow down during the second year of life. There is quite a lot of variation in how different stages of the illness progress but there is a gradual slowing of normal milestones and eventually a loss of skills that have been acquired. Loss of vision tends to start at around 18 months and usually progresses fairly rapidly. Alongside this is deterioration in mental functions, there is developmental regression or loss of skills e.g. speech, coordination, continence. These become apparent around this time or within a few months. Ataxia or clumsines increases as motor skills decline. Abnormal limb and body movements can occur and lead to spasticity which is continued muscle contraction and exaggerated reflexes. Epileptic seizures of various kinds can occur but tend to be mainly myoclonic jerks. Feeding becomes
more difficult with resulting poor weight gain and frequent symptoms of aspiration or difficulty coordinating swallowing .  Most children now receive nutritional support using a nasogastric or gastrostomy tube.

In spite of this deterioration in all faculties, children with INCL are able to smile, laugh and enjoy the presence of familiar people and music. If the medication is managed well then these abilities are preserved until death, which usually takes place at the age of 8-13 years.

Diagnosis

Diagnostic investigations may include neurophysiology tests, samples for microscopy (biopsy - usually skin [taken from perhaps the arm under local anaesthetic]) and genetic analysis. Blood samples may now also be collected for enzyme assay; this can now give the diagnosis without the need.

Treatment

Therapy for children with classic INCL is essentially supportive. Most INCL patients need medication from the first stage onwards throughout life. Attention to posture, seating, skin and mouth care is essential, with professional guidance from physiotherapists and occupational therapists.  Most children will require nutritional support at some stage.

As with all forms of NCL research continues into potential therapies for the disease.

The BDFA produce a leaflet  with more details about Infantile Batten Disease (INCL) and it can be downloaded.  If you would like a copy posted to you then please contact us.