Neuronal Ceroid Lipofuscinoses

Background and History: 

The neuronal ceroid lipofuscinoses or NCLs are a group of inherited neurodegenerative disorders in which defects in enzymes lead to an accumulation of specific molecules in cells leads to degeneration of nerve cells.  This group of disorders is considered to be the most common cause of progressive neurological and visual deterioration.  Mutations in at least 9 genes have been identified. 

Clinical Correlations: 

There is a wide range in the age of onset.  Neurological damage may be evident at birth in some cases whereas the disease is not evident until the 5th and 6th decades in others.  At some point in all individuals there is evidence of intellectual and movement (motor) deterioration.  Unsteadiness, seizures and loss of vision are usually evident at some point.  Eye examinations reveal damage to the optic nerve and dysfunction of the retina is demonstrable by an electroretinogram (ERG).  Night blindness, a decrease in side vision, and eventually loss of light perception are important symptoms.  The neurological deterioration is relentless and early death eventually follows.

Although the age of onset is a factor in the diagnosis and prognosis, it is necessary to do a gene test to determine which type of NCL is responsible for the clinical picture. 

Genetics: 

Virtually all types of CNLs are inherited in an autosomal recessive pattern although an autosomal dominant pattern can be seen in some families with an adult onset of disease.  However, in the majority of families both unaffected parents are carriers of the responsible mutation and disease results when children inherit two copies of the mutation.  A gene test is necessary to determine which type of disease is present. 

Diagnosis and Prognosis: 

The diagnosis usually requires a collaborative effort among pediatricians, pediatric neurologists, and ophthalmologists.  The combination of intellectual deterioration, seizures and visual impairment suggest the diagnosis.  Brain imaging and tests of retinal function (ERGs) combined with the clinical findings can confirm the clinical impression.

The prognosis is variable and a gene test to determine the specific mutation can be helpful in the determination of prognosis. 

Additional Information