Mucolipidosis II (MLII) is a rare lysosomal storage disease due to the deficiency of N-acetylglucosaminyl 1-phosphotransferase which results in the defective lysosomal targeting of several lysosomal enzymes. The multiple enzyme deficiencies cause accumulation of fatty substances (mucolipids) and complex carbohydrates (mucopolysaccharides) within the cells of many tissues of the body leading to abnormal cell architecture. However, the most affected system is the skeletal system that has abnormal trabeculation of bone and cartilage. The disease onset is during the first months of life, or sometimes even during the intrauterine period. The main features of MLII are hypertrophic gingiva and enlarged tongue, coarse facies, hirsutism, hernias, cutaneous infiltration, limited joint mobility, dysostosis multiplex, hepatosplenomegaly, corneal opacities, deafness, mental and motor retardation, and dwarfism. Mostly, the patients die in the childhood due to cardiorespiratory complications. The lysosomal enzyme activities show an unusual increase in the serum and urine, while they are decreased in cultured fibroblasts. The patients' fibroblasts have phase-dense intracytoplasmic inclusions, therefore, these cells are termed inclusion cells (I-cells) and MLII is also known as I-cell disease.
Mucolipidosis II (MLII) is caused by a mutation in the N-acetylglucosamine-1-phosphate transferase, alpha and beta subunits (GNPTAB) gene that leads to a deficiency in the enzyme N-acetylglucosaminyl 1-phosphotransferase. The normal enzyme is composed of three polypeptide subunits (alpha, beta, and gamma) which are encoded by two different genes. In MLII, the alpha and beta subunits are altered due to mutations in the GNPTAB gene.