a case study by McKenzi Shelton

1. What’s wrong with
Hannah?
McKenzi Shelton

2. Case study
Hannah Avromovitch just had her first birthday.
She was brought in to the clinic with mental-motor deterioration, convulsions,
and hypotonia.
Her parents say this began very recently.

3. What is your initial
diagnosis?

4. What tests do you perform
to confirm your diagnosis?

Upon examination it was
found that Hannah's eye
has a retinal cherry red
spot

5. What questions do you
ask her parents?

6. Background information
Hannah’s family is Ashkenazi Jewish
Hannah’s parents are first cousins
The Avromovitches have had two children that died a few years after
experiencing these symptoms in infancy

7. diagnosis
Hannah has Tay-Sachs disease
 Also called GM2 gangliosidosis I
Infants become nonresponsive to stimulation, suffer from seizures, various
forms of motor and neuron degradation, and ultimately death
Caused by a mutation in the HEXA gene
 Encodes alpha subunit of beta-hexosaminidase
 Produces ganglioside accumulation in lysosomes (neurons)
 Destructive
Carriers can be identified by an enzyme assay (blood test)
 Measures level of Hex-A in blood
 Carriers have low levels of Hex-A

8. Biochemistry of tay-sachs

Inability to properly degrade beta-hexosaminidase

Beta-hexosaminidase
 Enzyme
 Dimer

Alpha and beta subunits

Normally, a GM2 activator protein binds tgo GM2 gangliosides and
hexosaminidase before digestion of the sphingolipids occurs

If the sphingolipids are not digested the lysosomes become engorged and
eventually choke off needed cellular functions

9. Structures

HexA and GM2 activator on GM2 gangliosides

Crystalline structure of
human beta-
Hexosaminidase A

10. Do you know someone,
including yourself, that has
tay-sachs?

11. Occurrence of tay-sachs
High incidence in Ashkenazi Jews
 Three mutations that are present in high frequency
Both parents must be carriers
 1 in 250 of US population is a carrier
 1 in 50 Irish Americans are carriers

12. Treatments
There is no cure
Symptomatic treatment given
Enzyme replacement and gene therapies under trial

13. Sources
https://www.ncbi.nlm.nih.gov/pubmed/7732608
http://www.namrata.co/case-study-taysachs-disease/
http://chemistry.gravitywaves.com/chemistry/faculty/nsturm/CHE452/14_Bio
chem%20of%20Disease.htm
https://www.ncbi.nlm.nih.gov/pubmed/1834320
http://themedicalbiochemistrypage.org/taysachsdisease.php
http://019221f.netsolhost.com/carrierstats.shtml