GAUCHER’S 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 ½ Years of age- Epistaxis- Pallor- Bone pains• 3 ½ 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/gauchers.htm

• http://apamedcentral.org/Synapse/Data/PDFData/0012AMP/amp-43-1-33.pdf

• http://www.gaucherdisease.org/symptoms.php

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THANK YOU!