Mucolipidosis type II—also known as “I-cell disease”—is a rare life-threatening condition in which the heart and abdomens become swollen, bones deform, and the patient typically does not make it past the age of 7. This lysosomal storage disease is heritable and currently incurable.  

Inclusion cells are non-living substances located in the cell that are not membrane-bound. These non-living substances include glycogen, lipids, and pigments. In mucolipidosis, inclusion cells in growing fibroblasts occupy the cytoplasmic space aside the Golgi apparatus—hence the name “I-cell disease.”

Recent research reveals a new gene, TMEM251, that is defective in humans with symptoms of mucolipidosis type II. TMEM251 is crucial in enabling lysosomes to function appropriately. In AP Biology class, we covered how lysosomes are essential to various cell processes, such as digesting food and breaking down old cell parts enclosed in vesicles. Without the lysosome’s function, this waste will build up, unable to be broken down.

Several enzymes inside lysosomes digest worn-out cell parts (proteins, carbohydrates, lipids, and nucleic acids) of which the lysosome recycles. These enzymes require a signal called the mannose-6-phosphate biosynthetic pathway (M6P) in order to enter the lysosome. TMEM251 activates the M6P. When TMEM251 is defective, there is no M6P to allow the enzymes into the lysosome, thus creating an inability for the lysosomes to function

Researchers tested the link between defective TMEM251 and type II mucolipidosis symptoms by knocking this gene out in zebrafish, ultimately yielding defects in the zebrafish’s abdomen, heart, and skeletal development. These symptoms align with those of mucolipidosis type II in humans, concluding the existence of a relationship between TMEM251 and the disease. 

To treat children with mucolipidosis type II, the researchers propose the idea of “enzyme replacement therapy.” They hypothesize that by supplying enzymes containing M6P modification to TMEM251-deficient cells, the enzymes will be able to filter into the cell through endocytosis, delivering them to the malfunctioning lysosomes. Isn’t that neat? In AP Biology class, we learned that endocytosis occurs when the substances surrounding the cell membrane are transported into the cell. Through the process of receptor-mediated endocytosis, specific ligands (i.e. enzymes) bind to receptors that match their shape.  

A depiction of various types of Endocytosis

I believe that enzyme replacement therapy would efficiently treat mucolipidosis in humans, and encourage further study in this area to seek treatment for this deadly disease that robs young children of their bright futures. Would you support further research in this area? Please feel free to share your thoughts in the comments! 


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