I-cell disease is a rare lysosomal storage disorder that presents in early childhood with severe skeletal abnormalities and failure to thrive. A mutation in the GNPTA gene causes a deficiency in the enzyme uridine diphosphate (UDP)-N-acetylglucosamine-1-phosphotransferase.
- Autosomal recessive
- Prevalence: approximately 1 in 100,000–400,000 live births
- Male = female
- Disease most common in Japan
- Mutation of GNPTA gene: located on long arm of chromosome 4 (4q21-q23)
- Phosphodiesterase deficiency: rare
- GNPTA mutation causes UDP-N-acetylglucosamine-1-phosphotransferase deficiency.
- Causes lysosomal targeting disfunction → lysosomal enzymes are erroneously transported to extracellular matrix
- These enzymes do not function outside of acidic lysosomes.
- Lysosomes lack requisite enzymes for metabolism of absorbed cellular debris → debris accumulates within the cell, forming inclusion bodies:
- Fatty substances: mucolipids
- Complex carbohydrates: mucopolysaccharides
- Symptoms result from accumulation of mucolipids and mucopolysaccharides.
Clinical features evident by 6 months of age:
- Coarse facial features (often present at birth)
- Craniofacial abnormalities (often present at birth)
- Restricted joint movement
Patients present in 1st year of life with:
- Severe psychomotor retardation
- Congenital hip dislocation
- Inguinal hernias
- Gingival hypertrophy
- Skeletal manifestations (kyphoscoliosis, lumbar gibbus)
Progressive, severe psychomotor impairment leads to death in early childhood.
- Amniocentesis or chorionic villus sampling
- Low levels of UDP-N-acetylglucosamine-1-phosphotransferase enzyme activity is diagnostic.
Diagnostic tests performed after delivery:
- Elevated plasma lysosomal enzyme concentration and low level of lysosomal enzymes in cultured fibroblasts
- Inclusion bodies visible in peripheral blood lymphocytes
- Low levels of UDP-N-acetylglucosamine-1-phosphotransferase enzyme activity
No curative treatment is available for I-cell disease. Management is symptomatic and supportive:
- Nutritional supplements are recommended: iron and vitamin B12
- Physical therapy to slow degeneration of motor function
- Speech therapy
- Hip replacement and other orthopedic surgeries may be recommended to maintain mobility.
- Hearing aids
Bone marrow transplantation may be helpful as a remedy for neurologic degeneration (currently under investigation).
Genetic counseling should be offered to families considering having additional children.
- Hurler syndrome (mucopolysaccharidosis type I): rare lysosomal storage disease caused by deficiency in enzyme alpha-L-iduronidase, which causes accumulation of mucopolysaccharides in various body tissues. Infants appear normal at birth, but they develop symptoms within the 1st year of life. These symptoms include skeletal abnormalities, abdominal and inguinal hernias, coarse facial features, severe intellectual disability, and loss of developmental milestones. As the patient ages, further symptoms become evident, including joint contractures, vision/hearing deficits, and cardiac dysfunction. The condition is fatal; 5 years is the average age at death.
- Sialidosis (mucolipidosis I): very rare autosomal recessive lysosomal storage disease caused by deficiency in enzyme alpha-neuraminidase leading to pathologic accumulation of oligosaccharides. There are 2 forms of sialidosis. Type 1 presents later in life with involuntary muscle contractions and cherry-red macules in the retina. Type 2 presents during infancy with skeletal dysplasia, intellectual disability, and hepatosplenomegaly. Treatment is supportive.
- Pseudo-Hurler polydystrophy (mucolipidosis III): autosomal recessive lysosomal storage disease caused by a defect in UDP-N-acetylglucosamine-1-phosphotransferase and leading to accumulation of mucopolysaccharides and mucolipids. Symptoms are similar to, but less severe than, those of I-cell disease and include progressive stiffness, hip dysfunction, growth delay, intellectual disability, and mildly coarse facies. Treatment is supportive and similar to that for I-cell disease.
- Edmiston, R., Wilkinson, S., Jones, S., Tylee, K., Broomfield, A., Bruce, I. A. (2019). I-cell disease (mucolipidosis II): a case series from a tertiary paediatric centre reviewing the airway and respiratory consequences of the disease. JIMD Rep 45:1–8.
- Khan, S. A., Tomatsu, S. C. (2020). Mucolipidoses overview: past, present, and future. Int J Mol Sci 21:6812.
- National Organization for Rare Disorders. I cell disease. Retrieved April 28, 2021, from https://rarediseases.org/rare-diseases/i-cell-disease/
- Beck, M., Barone, R., et al. (1995). Inter- and intrafamilial variability in mucolipidosis II (I-cell disease). Clin Genet. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1399-0004.1995.tb03958.x