General description

I-cell disease, also known as mucolipidosis II, represents a severe autosomal recessive lysosomal storage disorder that fundamentally disrupts cellular enzyme trafficking mechanisms. The fundamental pathophysiological mechanism of I-cell disease involves a critical deficiency in the enzyme uridine-diphosphate N-acetylglucosamine: lysosomal-enzyme-N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase). This enzyme plays an essential role in the normal trafficking of lysosomal enzymes from their site of synthesis in the endoplasmic reticulum to their final destination within lysosomes.

Clinical manifestations

I-cell disease presents as a severe multisystem disorder with clinical manifestations that typically become apparent within the first year of life, often by six months of age. The disease shares many clinical similarities with Hurler syndrome but demonstrates an earlier onset, more rapid progression, and notably does not exhibit mucopolysacchariduria.

Growth retardation represents one of the most consistent early features, with linear growth typically ceasing by the second year of life and final adult height rarely exceeding 80 centimeters. The characteristic facial dysmorphism includes coarse features with periorbital puffiness, a flat and broad nasal bridge, anteverted nares, and progressive development of what has been described as gargoyle-like features.

Skeletal abnormalities are a major clinical feature, with patients exhibiting dysostosis multiplex, a distinct pattern of bone changes. These include early-onset craniosynostosis, beaked thoracolumbar vertebrae, broad ribs with periosteal reactions, pelvic dysplasia, and delayed epiphyseal ossification. Progressive joint contractures and restricted mobility often result in loss of independent ambulation. Carpal tunnel syndrome is also common and may require surgical intervention.

Neurological involvement is significant, with nearly universal profound psychomotor retardation. Some patients may achieve early milestones such as sitting, but few progress to walking or speaking. Progressive neurodegeneration, particularly involving cerebellar Purkinje cells, contributes to ataxic gait. Intellectual disability typically ranges from mild to moderate. Severe language delays are consistent, with most patients failing to develop meaningful verbal communication.

Cardiovascular complications include hypertrophic cardiomyopathy and valvular abnormalities due to storage material accumulation in cardiac tissues. Respiratory issues—including recurrent pneumonia, bronchitis, and otitis media—are common and often life-limiting. Together with cardiac dysfunction, these are the most frequent causes of death, typically occurring within the first decade of life.

Additional features include organomegaly (hepatosplenomegaly), umbilical and inguinal hernias, gingival hyperplasia, and obstructive sleep apnea.