What Causes It?
In 1934, the French chemist A. Aghion discovered the chemical cause of
the enlarged spleens and liver:
a buildup of a lipid (fatty substance) called "glucocerebroside."
This discovery led researchers to speculate why there was too much lipid
- did people with Gaucher disease make too much of the lipid for their
bodies to handle? Or did their bodies not break it down and dispose of
it? The answer to this question came during the early 1960s, when Dr.
Roscoe Brady's group showed that people with Gaucher disease made the
lipid normally but did not make enough of the enzyme
"glucocerebrosidase" to break it down and clear it out of the
body.
In 1967, Brady's group developed a convenient diagnostic test for Gaucher
disease which works by measuring the activity of the enzyme glucocerebrosidase
in white blood cells. The amount of enzyme
one's body makes directly relates to how severe a case of Gaucher disease
one has. The enzyme activity is also one way that may help to distinguish
the three types of Gaucher disease described in this chart.
The Three Types of Gaucher Disease |
|
Type 1 |
Type 2 |
Type 3 |
Whom it Strikes |
young adults/adults |
infants |
children/young adults |
Distinguishing symptom |
no nervous system problems |
early nervous system problems |
later onset of nervous system problems |
Effects of disease |
varies from mild to severe |
dies in infancy |
becomes severe |
Glucocerebrosidase Activity |
some activity but much less than normal |
very little activity |
little activity |
The next question of course was "Why do some people make too little
enzyme?" The answer to this question came in 1987, when the first
gene mutation that causes Gaucher disease
was discovered by Dr. Shoji Tsuji and coworkers.
Gaucher disease turned out to be an "autosomal recessive"
genetic disease. This means that both of the glucocerebrosdiase genes
a person inherits - one from the mother
and one from the father -- must be mutated for the person to have the
disease. A person with only one mutated gene
is a carrier. A carrier of Gaucher
Disease is not affected but can pass the trait on to his/her children.
The inheritance diagrams below show how a child can be affected depending
on the genetic material s/he inherits from her/his parents.
G = mutated gene
g = normal gene |
OPTION 01 |
Parent 1 (a carrier) Gg
|
Parent 2 (a carrier) Gg
|
Possibilities for each child they have
GG two mutated genes; person with Gaucher disease
Gg carrier of Gaucher gene; no signs or symptoms
gG carrier of Gaucher gene; no signs or symptoms
gg two normal genes; normal enzyme activity,
not a carrier |
OPTION 02 |
Parent 1
(a person with Gaucher disease)
GG |
Parent 2
(a person with normal genes)
gg |
Possibilities for each child they have
GG carrier of Gaucher gene; no signs or symptoms
Gg carrier of Gaucher gene; no signs or symptoms
gG carrier of Gaucher gene; no signs or symptoms
Gg carrier of Gaucher gene; no signs or symptoms |
OPTION 03 |
Parent 1 (a carrier) Gg
|
Parent 2
(a person with normal genes)
gg |
Possibilities for each child they have
GG two mutated genes; person with Gaucher disease
Gg carrier of Gaucher gene; no signs or symptoms
gG carrier of Gaucher gene; no signs or symptoms
gg two normal genes; normal enzyme activity,
not a carrier |
In the early 1970s, Dr. Brady's group devised an enzymatic test based on the enzyme's
activity to tell people if they were carriers or not, and a procedure
for prenatal diagnosis. These tests
give people information about their genetic status so that they can prepare
for the future.
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