TSD Presentation

START

By Nithusha S, Maaduri A, Alice F and Harry J

Tay-Sachs Disease

Histopathology

Pathophysiology

Med. Process

Index

Inheritance

Intro

Case Study

What it is and its causes

1. Introduction to TSD

• Also known as GM2 Gangliosidosis Type 1
• Lysosomal storage disorder that results in the destruction of nerve cells in the CNS
• Leads to the progressive symptoms in the CNS

What is TSD?

• Absence of beta-hexosamindase A enzyme that breaks down gangliosides
• Gangliosides build up to toxic levels in CNS which affects the function of the nerve cells

Causes of TSD

HEXA location

• Mutation in the HEXA gene, which encodes for beta-hexosaminidase A
• HEXA is located at 15q23

Etiology

Epidemiology and inheritance

2. Inheritance of TSD

• Rare in general population
• Incidence in 1 in 100, 000 live births
• Carrier frequency is about 1 in 250

• Occurs in isolated, inbred populations:
• Ashkenazi Jews
• 1 in 29 carriers
• 1 in 3500 affected
• French Canadian
• Amish
• Cajun

Epidemiology

• Autosomal recessive
• To have the disease, mutation in both copies of HEXA gene
• Parents are only carriers of disease
• Chances of:
• Non-carrier 25%
• Unaffected carrier 50%
• Affected 25%

Inheritance

Symptoms, diagnosis and treatment

3. Medical Process

Late Onset/ Adult

Juvenile

Infantile

Least severe and commonLifespan varies from shorterned to unaffected

Symptoms appear anytime in childhood, but usually between ages 2 to 5

Most severe and commonChildren can only live up to 3-5 years

Symptoms

• Blood test for beta-hexosaminidase A enzyme
• Molecular genetic testing of HEXA gene

Diagnosis

• No cure, treatments involve supportive care to manage symptoms
• Neurologists: Manage seizures
• Gastroenterologists, surgeons and nutritionists: Manage feeding
• Occupational/ Physical therapists: Assist with daily living and mobility
• Therapeutic modalities:
• Enzyme Replacement Therapy
• Enzyme Enhancing Therapy
• Substrate Reduction Therapy
• Gene Therapy
• Bone Marrow Transplantation

Treatment

4. Pathophysiology

• Deficiency of beta hexosaminidase which is responsible for GM2 ganglioside degradation
• There are three proteins required to make hexosaminidase:

• Alpha subunits
• Beta subunits
• GM2 activator protein
• HEXA gene encodes for alpha sub-unit of this enzyme
• GM2 gangliosides accumulate in the brain which leads to the symptoms of the disease

5. Histopathology

• Accumulation of glycosphingolipids leads to cells in CNS to die, triggering an inflammatory response
• GM2 ganglioside accumulation in retinal ganglion cells cause cherry red spots on the retina

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