Classical Late Infantile Onset NCL

The mutation in the CLN2 gene causes a deficiency of an enzyme called  (Tri-peptidase-1, TPP1). This enzyme is involved in breaking down small proteins within the lysosome. The lack of TPP1 leads to a build up of waste products in the cell. Eventually the cells die. This accumulation
of this material in cells can be seen with a powerful electron microscope and are known as curvilinear bodies (CVB).

Age at onset and first symptoms

The onset of symptoms that reach the attention of doctors is often between 2 and 4 years of age. Prior to this many parents recognise delayed speech and some children may have been referred for speech therapy. The major symptoms that bring children to medical attention are  seizures, ataxia [clumsiness] and myoclonus [jerks, drop attacks]. The epileptic seizures usually herald the onset of further symptoms. Seizures may be varied and include Myoclonic jerks which may cause the child to fall, absence attacks when the child becomes vacant or full “grand mal” convulsions with loss of consciousness. Alongside these seizures is a deterioration in mental functions, there is developmental regression [loss of skills e.g. speech, coordination, continence] and this becomes apparent around this time or within a few months. Ataxia increases as motor skills decline. Abnormal limb and body movements can occur and lead to spasticity (continued muscle contraction and exaggerated reflexes). Sometimes the muscle spasticity can cause joint contractures. The examination findings do vary with the age of the child and the stage of  the disease. Initially the children have an ataxic gait [clumsy, unsteady walk]. As the disease progresses, the ataxia worsens and children develop frequent myoclonic jerks. Late in the course of the disease children are unable to walk or sit unsupported (generally around the age of 4 - 6 years). They lose language and vision (blindness is usually by 5 or 6 years), although many are able to recognise their parents’ voices. They respond to their parents and siblings with smiles. Feeding becomes more difficult with resulting poor weight gain and frequent symptoms of aspiration [difficulty coordinating swallowing with subsequent coughing or choking as food & drink “goes down the wrong way”]. Most children now receive nutritional support using a nasogastric or gastrostomy tube and this may prolong life. Death usually occurs in middle childhood between the ages of 5 and 14 years depending on the speed of disease progression.

Diagnosis

Usually children present to a paediatric neurologist because the seizures are frequent and becoming difficult to control with anticonvulsants, or because additional features have emerged. By this time, the diagnosis lies between NCL with a late infantile onset and other causes of
developmental regression and seizures. Often the child is beginning to have myoclonic jerks and is less able to walk because of worsening ataxia. The diagnosis of one of the NCLs is then straightforward and only a limited number of investigations are required.  Investigations may include neurophysiology (EEG, ERG, etc), 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 for
a biopsy.

Treatment

Therapy for children with classic LINCL is essentially supportive.  Attention to posture, seating, skin and mouth care is essential, with professional guidance from physiotherapists and occupational therapists. Chest physiotherapy may be needed intermittently to help clear infections. Most children will require nutritional support at some stage, and parents often find that the use of a nasogastric tube or gastrostomy tube makes life much easier.  Anticonvulsants are necessary from quite early in the course of the disease and many children eventually require more than one drug to control seizures. Even then control is not always achieved.

The BDFA produce a more detailed leaflet about LINCL which can be downloaded.  If you would like a copy posted to you, please contact us.

A mother of a child with Late Infantile Batten Disease talks about her family's experience.