GAUCHERS

DISEASE
Presented by:
Alexandra Regilyne M. Romero
History of Gaucher Disease
1882- French
physician, Philippe Charles
Ernest Gaucher (go-SHAY)
described a clinical syndrome
in a 32 yr. old women whose
liver and spleen were
enlarged.
History of Gaucher Disease
1924- German physician, H. Lieb isolated
a particular fatty compound from the
spleens of people with Gaucher disease.

1934- French physician, A. Aghion
identified this compound as
glucocerebroside.
History of Gaucher Disease
1965- American physician, Roscoe O.
Brandy demonstrated that the
accumulation of glucocerebroside results
from a deficiency of the enzyme
glucocerebrosidase.
What is Gaucher Disease?
Gaucher's disease is caused by a
deficiency of the enzyme
glucocerebrosidase, which helps the body
process the fatty substance
glucocerebroside.
The disease is sometimes called
glucocerebrosidase deficiency.
What is Gaucher Disease?
People with Gaucher disease lack the
normal form of the glucocerebrosidase,
and are unable to break down
glucocerebroside.
Instead, glucocerebroside remains stored
within the lysosomes, preventing the
macrophages from functioning normally.
What is Gaucher Disease?
Enlarged macrophages,
due to the accumulated
glucocerebroside, are
known as, Gaucher
cells.

The Mutation
Glucocerebrosidase gene locus 1q21
Amino acid substitution of serine for
asparagine.
Transient expression studies following
oligonucleotide-directed mutagenesis of
the normal cDNA confirmed that the
mutation results in loss of
glucocerebrosidase activity.
Inheritance Patterns
Gaucher disease is a autosomal recessive
trait.
Gaucher carriers have have one normal
copy of the glucocerebrosidase gene and
one defective copy.
Since the trait is autosomal, Males and
Females have an equal chance of
inheriting the defective gene.
Gaucher Diseases
Gaucher specialists divide the disease into
3 classifications based on the particular
symptoms and course of the disease.

Type 1, Adult Gaucher Disease
Type 2, Infantile Gaucher Disease (Rare)
Type 3, Juvenile Gaucher Disease (Rare)
Type 1, Adult Gaucher Disease
Most common form.
Defective gene for glucocerebrosidase
occurs in 1 in 100,000 people in the
general population.
More common among Ashkenazi Jews,
occurring in 1 in every 850 births
Type 1 Symptoms
Splenomegaly
Hepatomegaly
Bone disease
Thrombocytopenia
Growth retardation


Type 1 Symptoms
Bruising/ Bleeding
Anemia
Fatigue
Bone pain/ crisis
Abdominal pain
Type 2 and Type 3
Types 2 and 3 Gaucher disease are known
as neuronopathic forms of the disorder
because they are characterized by
problems that affect the central nervous
system.
Type 2 Gaucher disease usually causes life-
threatening medical problems beginning in
infancy. Type 3 Gaucher disease tends to
progress more slowly than type 2.
Type 2 Symptoms
liver and spleen
enlargement are
apparent by 3 months
of age.
Individuals usually die
before 2 years of age
Type 3 Symptoms
Liver and spleen enlargement is variable,
and signs of brain involvement such as
seizures gradually become apparent.
Skeletal irregularities
eye movement disorders
Seizures
respiratory problems
and blood disorders.
Treatment
Enzyme Replacement Therapy
Bone marrow transplantation
Surgery to remove the spleen
Blood transfusions
http://apamedcentral.org/Synapse/Data/PDFData/0012AMP/amp-43-1-33.pdf
First year and 6 months of
age, she started to have:
- Blank stares
- Hepotosplenomegaly
- Thrombocytopenia
2 years of age
- Pallor
- Peticchiae on the chest
- No erlenmeyer flask
deformity
PATIENT 2
2 Years of age
- Epistaxis
- Pallor
- Bone pains
3 years old
- Hepatosplenomegaly
- Erlenmeyer flask deformity
- Thrombocytopenia
a student performing below
average with mild mental
retardation.
http://apamedcentral.org/Synapse/Data/PDFData/0012AMP/amp-43-1-33.pdf
PATIENT 3
3 years of age
- Hematoma
- Hepatosplenomegaly
4 years of age
- Anemic
- Thrombocytopenic
- Erlenmeyer flask deformity

Currently an average performing
student with mild mental
retardation.
http://apamedcentral.org/Synapse/Data/PDFData/0012AMP/amp-43-1-33.pdf
Results of treatment
With enzyme replacement therapy, the
hemoglobin values normalized after 8 months
for Patient 1 and after 2 months for patient 2
and 3.
Platelet counts increased to normal levels
after 18 months for patient 1 and 7 months for
patient 2.
The enlarged liver and spleen have
diminished to near normal sizes after 2 years
of ERT.
The clinical response of bone disease to
ERT has been reported to be favorable
with the disappearance of bone crises and
new fractures under ERT, and marked
reduction in the intensity and frequency of
bone pain
References
http://www.actamedicaphilippina.com.ph/content
/genotype-phenotype-correlations-filipino-
patients-type-3-gaucher-disease
http://www.ninds.nih.gov/disorders/gauchers/gau
chers.htm
http://apamedcentral.org/Synapse/Data/PDFDat
a/0012AMP/amp-43-1-33.pdf
http://www.gaucherdisease.org/symptoms.php

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