CLN1 disease
CLN1 disease is an inherited disorder that primarily affects the nervous system, leading to developmental regression, seizures, and vision loss.
Overview
CLN1 disease is an inherited disorder that primarily affects the nervous system. Individuals with this condition typically have normal development in infancy, but by 18 months, they often become increasingly irritable and begin to lose previously acquired skills, a process known as developmental regression. Over time, brain cells die, leading to brain atrophy and an unusually small head. Affected children typically experience hypotonia (decreased muscle tone), intellectual and motor disability, and rarely gain the ability to speak or walk.
Symptoms
Symptoms often progress as the disease worsens. Common clinical features include:
- Developmental regression
- Irritability
- Hypotonia
- Repetitive hand movements
- Myoclonus (muscle twitches)
- Epilepsy (recurrent seizures)
- Vision loss
- Frequent respiratory infections
- Severe feeding difficulties, often requiring a feeding tube
In later-onset cases, which may manifest in childhood or adulthood, individuals experience a decline in intellectual function, myoclonus, epilepsy, and vision loss. Adults may also exhibit movement disorders, such as ataxia (impaired muscle coordination) or parkinsonism.
Causes
CLN1 disease is caused by mutations in the PPT1 gene, which provides instructions for making an enzyme called palmitoyl-protein thioesterase 1. This enzyme is active in lysosomes, the cell compartments responsible for digesting and recycling molecules. The enzyme removes long-chain fatty acids from certain proteins to facilitate their breakdown. Mutations in PPT1 decrease or eliminate the function of this enzyme, causing partially broken-down fats and proteins to accumulate in lysosomes, which is particularly damaging to nerve cells.
Inheritance
This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but typically do not show signs or symptoms of the condition.