Whats wrong with Hannah?McKenzi Shelton
Case studyHannah 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.
What is your initial diagnosis?
What tests do you perform to confirm your diagnosis?Upon
examination it was found that Hannah's eye has a retinal cherry red
spot
What questions do you ask her parents?
Background informationHannahs family is Ashkenazi Jewish
Hannahs parents are first cousins
The Avromovitches have had two children that died a few years
after experiencing these symptoms in infancy
diagnosisHannah 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
Biochemistry of tay-sachsInability 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
Structures HexA and GM2 activator on GM2 gangliosides
Crystalline structure of human beta-Hexosaminidase A
Do you know someone, including yourself, that has tay-sachs?
Occurrence of tay-sachsHigh 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
Treatments There is no cure
Symptomatic treatment given
Enzyme replacement and gene therapies under trial
Sourceshttps://www.ncbi.nlm.nih.gov/pubmed/7732608
http://www.namrata.co/case-study-taysachs-disease/
http://chemistry.gravitywaves.com/chemistry/faculty/nsturm/CHE452/14_Biochem%20of%20Disease.htm
https://www.ncbi.nlm.nih.gov/pubmed/1834320
http://themedicalbiochemistrypage.org/taysachsdisease.php
http://019221f.netsolhost.com/carrierstats.shtml
