Palmitoyl-protein thioesterase deficiency

Palmitoyl-protein thioesterase deficiency

Palmitoyl-protein thioesterase deficiency, also known as Infantile Neuronal Ceroid Lipofuscinosis (INCL) or CLN1 disease, is a rare, inherited neurodegenerative disorder that primarily affects the nervous system. It is one of a group of disorders known as the neuronal ceroid lipofuscinoses (NCLs), which are characterized by the accumulation of lipopigments in the body's tissues.

Pathophysiology

Palmitoyl-protein thioesterase deficiency is caused by mutations in the PPT1 gene, which provides instructions for making an enzyme called palmitoyl-protein thioesterase 1. This enzyme is involved in the breakdown of fatty acids (palmitate) from proteins, a process that is essential for normal cellular function. When the PPT1 enzyme is deficient or absent, fatty acids accumulate in the lysosomes, leading to cell damage and the symptoms of the disease.

Clinical Features

The symptoms of palmitoyl-protein thioesterase deficiency typically begin in infancy. Affected children may initially appear normal but gradually lose previously acquired skills such as crawling, walking, and talking. Other symptoms include:

• Seizures
• Visual impairment leading to blindness
• Muscle weakness and atrophy
• Cognitive decline
• Behavioral changes

The progression of the disease is rapid, and most children with this condition do not survive beyond early childhood.

Diagnosis

Diagnosis of palmitoyl-protein thioesterase deficiency is based on clinical evaluation, family history, and specialized tests. These may include:

• Enzyme assay to measure PPT1 activity in leukocytes or fibroblasts
• Genetic testing to identify mutations in the PPT1 gene
• Brain imaging studies such as MRI to detect characteristic changes

Treatment

Currently, there is no cure for palmitoyl-protein thioesterase deficiency. Treatment is primarily supportive and symptomatic, focusing on managing seizures, nutritional support, and physical therapy to maintain mobility as long as possible. Research into potential therapies, including gene therapy and enzyme replacement therapy, is ongoing.

Prognosis

The prognosis for individuals with palmitoyl-protein thioesterase deficiency is poor, with most affected children experiencing severe neurological decline and early death. However, the course of the disease can vary, and supportive care can improve quality of life.

Also see

• Neuronal ceroid lipofuscinosis
• Lysosomal storage disease
• Genetic disorders