I-cell disease

I-cell disease, also known as mucolipidosis II, is a rare inherited metabolic disorder characterized by a deficiency in the enzyme required for the proper functioning of lysosomes. This condition is caused by mutations in the GNPTAB gene, which leads to the accumulation of certain substances within the cells, forming inclusion bodies, or "I-cells."

Signs and symptoms

Individuals with I-cell disease typically present with symptoms in infancy. These symptoms may include:

• Developmental delay
• Coarse facial features
• Skeletal abnormalities
• Growth retardation
• Enlarged liver and spleen (hepatosplenomegaly)
• Heart valve abnormalities

Cause

I-cell disease is caused by mutations in the GNPTAB gene, which encodes the enzyme N-acetylglucosamine-1-phosphotransferase. This enzyme is crucial for the proper tagging of lysosomal enzymes with mannose-6-phosphate, a marker that directs these enzymes to the lysosomes. Without this marker, lysosomal enzymes are misdirected outside the cell, leading to the accumulation of undigested substrates within the lysosomes.

Diagnosis

Diagnosis of I-cell disease is based on clinical evaluation and confirmed through genetic testing. Laboratory findings may show elevated levels of lysosomal enzymes in the blood and other body fluids, as these enzymes are not properly transported to the lysosomes.

Differential diagnosis

Conditions that may present similarly to I-cell disease and should be considered in the differential diagnosis include:

• Hurler syndrome
• Hunter syndrome
• Mucolipidosis III

Treatment

There is currently no cure for I-cell disease. Treatment is primarily supportive and focuses on managing symptoms and improving the quality of life. This may include:

• Physical therapy
• Occupational therapy
• Surgical interventions for skeletal abnormalities
• Management of cardiac issues

Prognosis

The prognosis for individuals with I-cell disease is generally poor. Most affected individuals have a significantly shortened lifespan, often not surviving beyond early childhood due to complications such as respiratory infections and heart disease.

Related pages

• Lysosomal storage disease
• Hurler syndrome
• Hunter syndrome
• Mucolipidosis III
• Genetic mutation
• Inherited metabolic disorder