Gaucher Disease

Question 1

Who discovered Gaucher Disease?

Answer 1

Philippe Gaucher discovered this disease in 1882

Question 2

How many individuals does Gaucher disease affect?

Answer 2

Gaucher disease affects around 1:50,000 of the general population but appears with greater frequency in the Ashkenazi Jewish populations with frequencies as high as 1:850

Question 3

What enzyme is deficient in individuals with Gaucher disease?

Answer 3

Glucocerebrosidase

Question 4

Mutations in what gene are associated with Gaucher disease?

Answer 4

Gaucher disease is caused by a deficiency of glucocerebrosidase within the lysosomes resulting from mutations in the GBA gene encoding this lysosomal hydrolase

Question 5

In what cell type does glucocerebroside accumulate due to its ineffective breakdown

Answer 5

Glucocerebroside accumulates in macrophage cells within the bone marrow, spleen and liver

Question 6

On what chromosome is the GBA gene located?

Answer 6

The GBA gene associated with Gaucher disease is located on the long arm of chromosome 1 at position 21 (1q21)

Question 7

In what fashion is Gaucher disease inherited?
A) Autosomal Dominant
B) Autosomal Recessive
C) X-linked Dominant
D) X-linked Recessive

Answer 7

Gaucher disease is inherited in an autosomal recessive manner meaning that individuals must receive two copies of a defective allele to show symptoms

Question 8

Mutations in the GBA gene have also been implicated in what other condition?

Answer 8

Mutations in the GBA gene have also been associated with Parkinson’s disease. There is evidence to suggest that Parkinson’s patients who carry mutations in the GBA gene are more severely affected and suffer from earlier onset of the condition

Question 9

How many sub-types of Gaucher disease are there?

Answer 9

Gaucher disease is split into three sub-types, Type 1, Type 2 and Type 3

Question 10

Of the three sub-types of Gaucher disease, which is the most common and what are the characteristic symptoms of Type 1 Gaucher disease.

Answer 10

Gaucher disease Type 1 is the most common and frequently presents in childhood.

Type 1 Gaucher disease is characterised by splenohepatomegaly anaemia and thrombocytopenia.

Question 11

Of the three sub-types of Gaucher disease, which is the most severe?

Answer 11

Type 2 Gaucher disease is the most severe form and is characterised by neurological complications (hypokinesia, hypotonia, and swallowing difficulties) and death in early childhood. Like all forms of Gaucher disease, individuals with Type 2 also suffer from splenohepatomegaly, anemia and thrombocytopenia

Question 12

In order to be transported to the lysosome, what receptor does glucocerebrosidase bind to in the endoplasmic reticulum?

Answer 12

Glucocerebrosidase binds to the LIMP-2 receptor in the endoplasmic reticulum before being packaged into clathrin coated vesicles and transported to the lysosome

Question 13

What are the three main forms of treatment available for individuals with Gaucher disease?

Answer 13

Enzyme Replacement Therapy

Substrate Reduction Therapy

Haematopoetic stem cell transplant

Question 14

Describe the features of Type 3 Gaucher disease

Answer 14

Horizontal saccade (rapid eye movements), strabismus (improper alignment of the eyes) hypertonia and swallowing difficulties.

In addition to the above individuals with Type 3 Gaucher disease also suffer from splenohepatomegaly, anemia and thrombocytopenia