Defective uptake of enzymes into lysosomes: I-cell disease (mucolipidosis type II)

Due to a mutation of the gene on chromosome 4
for the phosphotransferase needed to form the
mannose-6-phosphate recognition signal (see
p. 352), hydrolases cannot be taken up into lysosomes.
Unlike normal cultured fibroblasts (1),
those of patients (2) contain numerous densely
packed cytoplasmic inclusion bodies (thus, the
name I-cell disease). The vesicular inclusions
consist of hydrolases that cannot enter the lysosomes
because the mannose-6-phosphate recognition
signal is absent. Numerous enzymes
are missing from the lysosomes, while their
concentration in other parts of the cells and in
body fluids is increased. Patients (3) show a
severe progressive clinical picture, with the first
signs usually apparent in the first half-year of
life.