Infantile neuronal ceroid lipofuscinosis

A rare genetic neurodegenerative disorder

Infantile neuronal ceroid lipofuscinosis (INCL), also known as Santavuori-Haltia disease, is a rare, inherited neurodegenerative disorder that primarily affects infants and young children. It is one of the forms of neuronal ceroid lipofuscinosis (NCL), a group of disorders characterized by the accumulation of lipopigments in the body's tissues.

Pathophysiology

INCL is caused by mutations in the CLN1 gene, which encodes the enzyme palmitoyl-protein thioesterase 1 (PPT1). This enzyme is responsible for breaking down certain proteins in the lysosome, a cellular organelle involved in waste processing. Mutations in the CLN1 gene lead to a deficiency of PPT1, resulting in the accumulation of lipofuscin, a fatty substance, in the neurons and other cells. This accumulation disrupts normal cellular function and leads to the progressive degeneration of the nervous system.

Clinical Features

The symptoms of INCL typically begin between 6 months and 2 years of age. Early signs include developmental delay, seizures, and visual impairment. As the disease progresses, affected children may experience loss of motor skills, muscle weakness, and myoclonus. Vision loss progresses to blindness, and children with INCL often develop microcephaly and spasticity.

Diagnosis

Diagnosis of INCL is based on clinical evaluation, genetic testing, and the examination of tissue samples. A skin or tissue biopsy may reveal the characteristic accumulation of lipofuscin. Genetic testing can confirm mutations in the CLN1 gene. Electroencephalography (EEG) and magnetic resonance imaging (MRI) may also be used to assess the extent of neurological involvement.

Management

There is currently no cure for INCL, and treatment is primarily supportive. Management focuses on alleviating symptoms and improving quality of life. Anticonvulsants may be used to control seizures, and physical therapy can help maintain mobility. Supportive care may also include nutritional support and interventions to address vision and communication difficulties.

Prognosis

The prognosis for children with INCL is poor. The disease progresses rapidly, and most affected children do not survive beyond early childhood. The rate of progression and severity of symptoms can vary, but the condition is invariably fatal.

Research

Research into INCL is ongoing, with studies focusing on understanding the underlying mechanisms of the disease and developing potential therapies. Gene therapy and enzyme replacement therapy are areas of active investigation.

Related pages

• Neuronal ceroid lipofuscinosis
• Lysosome
• Genetic disorder
• Neurodegenerative disease