Mutations in GNPTAB cause mucolipidosis II and mucolipidosis III alpha/beta, which are inherited lysosomal storage disorders that slowly progress over time. People with these disorders lack an enzyme called GlcNAc-1-phosphotransferase which is important for the proper functioning of lysosomes, the digestive system of the cell. Mucolipidosis II is more severe because the enzyme is absent and mucolipidosis III alpha/beta is milder because very low levels of the enzyme are present.
Mucolipidosis II presents at birth with limited growth and skeletal abnormalities. Babies develop coarse facial features and thick gums in early infancy that become more prominent with age. Most affected children will have joint stiffening, hernias, malformed bones, microcephaly (small head and incomplete brain development), and severe learning difficulties. Heart abnormalities and respiratory insufficiency are the major causes of death. People with mucolipidosis II typically pass away in early childhood.
Mucolipidosis III alpha/beta presents around age 3 years when growth begins to slow. Individuals will usually be shorter than their unaffected family members. Affected children have coarse facial features that are less prominent and progress more slowly. Heart and respiratory complications are still the major cause of death. Individuals with mucolipidosis III alpha/beta are typically able to walk, though due to joint stiffening, may need to use a wheelchair by early adulthood. Intelligence and language development are typically normal, though many still require special education due to their physical limitations. Motor development is variable and may be normal to moderately delayed. People with mucolipidosis III alpha/beta usually live into early to mid adulthood.
Mucolipidosis II and mucolipidosis III alpha/beta are rare. They affect less than 1 in 100,000 individuals worldwide and may be more common in individuals from Portugal.
There is no cure for mucolipidosis II or III alpha/beta. Management of symptoms may include occupational therapy, speech therapy and low-impact physical therapy. Dental and audiologic management may be beneficial, but surgeries should be avoided to prevent airway complications and adverse reactions to anesthesia. Hip replacement has been helpful for some individuals with a milder disease course. For patients with mucolipidosis III alpha/beta, intravenous pamidronate may provide relief from bone density loss, joint pain, and immobility, but it is not a cure.
The prognosis for an individual with mucolipidosis II is poor, with death typically occurring in early childhood. Mucolipidosis III alpha/beta is more variable and many survive to early adulthood.
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