Lvsosomes in Health 
and Disease 
If the cell does not pro- 
duce a certain lysosomal 
enzyme or if an enzyme 
is not properly “addressed” 
in the Golgi apparatus, 
a lysosomal storage 
disease can result. These 
diseases are caused hy a 
massive accumulation of 
material that should 
have heen digested in the 
lysosome. Persons with 
the lysosomal storage 
disease known as 
Hurler’s syndrome, for 
example, cannot break 
down large molecules of 
sugar compounds called 
glycosaminoglycans 
because their lysosomes 
do not contain the 
enzyme iduronidase. 
Glycosaminoglycans 
accumulate in the lyso- 
somes, swelling them so 
much that the functioning 
of the entire cell is 
impaired. 
A particularly severe 
lysosomal disorder is 
known as I-cell disease. 
Children born with this 
disease lack the entire 
range of lysosomal 
enzymes. The enzymes 
are made, hut they are 
dumped outside the cell 
instead of being sent to 
the lysosomes. Various 
cellular nutrients thus 
cannot be digested and 
so pile up in dark lumps, 
called inclusion bodies, 
within the lysosomes. 
The disease affects the 
kidneys, heart, and 
nervous system, and 
children with it usually 
die of heart failure or 
pneumonia before reach- 
ing puberty. 
In the early 1970’s, 
Elizabeth Neufeld, who 
was then at the National 
Institutes of Health, 
showed that the lysoso- 
mal enzymes of persons 
with I-cell disease emerge 
from the Golgi apparatus 
without the chemical tag 
they need to he directed 
to the lysosomes. She also 
showed that the defect 
could be corrected in 
test-tube cultures of cells 
taken from people with 
the disease. The corrective 
factors she supplied were 
the specific, properly 
tagged enzymes that the 
cells lacked. 
Although enzyme 
replacement therapy is 
not being used to treat 
people with lysosomal 
storage diseases like 
Hurler’s syndrome, it is 
being used to treat a 
different group of disor- 
ders called lipid storage 
diseases. Enzyme 
replacement therapy for 
many disorders presents 
challenges to researchers, 
however, because purified 
enzymes injected directly 
into the body tend to he 
quickly destroyed or 
inactivated. It is particu- 
larly difficult to get 
enzymes into brain 
cells — an important 
problem now under 
investigation, since 
several lysosomal storage 
diseases produce severe 
mental retardation. 
