Genetic Disorders: Gaucher's Disease

HBio IMS, Jacobus, Per 3

Genetic Disorders: Gaucher's Disease

By: Anya Hughes | Research Doc

Timeline

the history behind Gaucher's Disease

1882

1927

1965

1901

1934

1980s

Dr. Nathan Brill finds alleles must be inherited from both parents, first to use name “Gaucher’s disease”

Philippe Charles-Ernest Gaucher performs autopsy, observes patient w/splenomegaly + enlarged cells -> discovers Gaucher’s disease (GD)

Henriette Aghion discovers glucocerebroside build-up = organomegaly (e.g. spleen, liver)

Neuronopathic Gaucher's Disease (Type 2 & Type 3) discovered

Dr. Edward Ginns discovers GBA gene mutation is cause for Gaucher's

Dr. Roscoe Brady / Dr. Patrick discover glucocerebrosidase enzyme only works at 10 - 20% activity

Sources

What might it look like?

Signs and Symptoms

• Type 1 Clinical Organ & Blood Signs: Anemia, Organomegaly, Bruising/Bleeding/Clotting issues, Fatigue, Lung Problems, Brown, pigmented skin spots
• Type 1 Clinical Bone Signs: Osteonecrosis, Osteoporosis, Osteopenia
• Type 2 & 3 Clinical Neurological Signs: Cognitive difficulties, unusual muscle movement/spasm, coordination problems
• General Symptoms: Pain, long-lasting bleeding, easy bruising, chronic fatigue, difficulty breathing, body aches
• Signs Family Members may Witness: difficulty walking, bone pain crises, lack of appetite, difficulty exerting large amounts of energy/staying alert/concentrating

Osteonecrosis of the hip / hepatomegaly & splenomegaly

Sources

Key

Scenario

Punnett

Important Info:

• Autosomal recessive disorder
• Affected offspring inherit two mutated recessive alleles (1 from each parent)

Key:

• Unaffected:
• Carrier:
• Affected:

Gg

GG

Gg

gg

Analysis

43

Gg

Heterozygous:

Jake and Samantha are shocked to find that their child has Gaucher’s disease. Curious as to how this could have happened, they go to get genetically tested, and find that Samantha is a carrier for Gaucher’s disease and Jake is unaffected. What is the chance Jake and Samantha’s next child will either have or be a carrier for Gaucher’s disease?

Homozygous Dominant:

Due to the fact that Jake is a heterozygous carrier like Samantha, their child will have a 50% chance of being a carrier for Gaucher's disease.

GG

Homozygous Recessive:

gg

Pedigree

Key

Unaffected:

Affected:

Carrier:

II

III

Demographic Stats

Treatments /Life Expectacy:

• Cultural Prevalence: Most prevalent in those w/ Ashkenazi Jewish (Eastern/Central European) heritage
• 1/450 are affected, 1/12 are carriers, Type 1 is most common
• Worldwide Statistics:
• 1/100,000 persons affected
• Type 3 more common than Type 2
• Trend: Types 2 & 3 -> more common in Egypt, India, Japan, Poland, and Sweden / Type 1 -> more common in Western areas

• Less effective: Liver transplants, Spleen removal
• Risky: Bone marrow transplants (successful in rare cases for people with type 1)
• Enzyme Replacement Therapy (ERT)
• Efficacy: According to a study, collectively, patients experienced a 96.55% reduction in events GD
• Limitations: Requires a medical professional, ups and downs, possible resistance via antibodies, ineffective for Type 2 and 3 GD patients
• Substrate Reduction Therapy (SRT)
• Efficacy: Effective, patients feel more consistent in terms of energy (no ups and downs)
• Limitations: More side effects than ERT, only available to Type 1 (and some Type 3) adults
• Impact on Life Expectancy for both: +10 - 15 yrs

Central Europe

Eastern Europe

Sources

Did you know...?

Interesting Facts

• Brian Berman - first to be successfully treated for Gaucher's disease in the 1970s
• Is now President and CEO of the National Gaucher Foundation (NGF)

• Dr. Gaucher was a dermatologist
• Gaucher's disease subsequent diseases
• Parkinson's Disease
• Cancer
• GD - Orphan Disease (affects less than 200,000 nationwide)

Sources

Thank You for Listening!

- Anya