Medical Presentation

1. Tay-Sachs Disease
(HEXA Mutation)
Autosomal Recessive
By Noel Christian
Group 6

2. PRINCIPLES
• Lysosomal storage disease
• Ethnic variation in allele frequencies
• Genetic drift
• Pseudo-deficiency
• Population screening

3. MAJOR PHENOTYPIC FEATURES
• Age at onset: infancy through adulthood
• Neurodegeneration
• Retinal cherry-red spot
• Psychosis

4. Disease Etiology and Incidence
 Tay-Sachs disease autosomal recessive disorder of ganglioside
(oligosaccharides) catabolism that is caused by deficiency of
hexosaminidase A.
 The enzyme deficiency varies widely among different populations; the
incidence of Tay-Sachs disease ranges from 1 in 3600 Ashkenazi Jewish
birth to 1 in 360,000 non–Ashkenazi Jewish North American births.

5. Pathogenesis
 Hexosaminidase A is a lysosomal enzyme composed of two subunits.
The α subunit is encoded by the HEXA gene on chromosome 15, and
the β subunit is encoded by the HEXB gene on chromosome 5.
 HEXA codes for the α subunit of the enzyme β hexosaminidase A.
 Mutations of the α subunit or the activator protein cause the
accumulation of GM2 in the lysosome and thereby Tay-Sachs disease

6. β Hexosaminidase A
 Normally β hexosaminidase A helps to degrade a lipid called GM2
ganglioside, but in the case, the enzyme is absent allowing excessive
accumulation of GM2 ganglioside in the lysosomes of the neurons.
 The large built up of gangliosides in the neurons of the brain results in
marked degenerative changes in the CNS & death occurs before 4 years
of age.

10. Frameshift Mutation

11. TYPES OF TAY-SACH DISEASE
(Phenotype)
Based on the onset age of neurological symptoms, the disease is classified
into several forms
 Infantile acute form:
 -Most common and fatal (by age of 5)
 Juvenile onset:
 -Anywhere from 6-16 yrs - crippling
 Adult/late onset:
 -30 to 40 yrs - life shortening - slower progressing

12. Infantile Tay-Sachs Disease
 Infants with Tay–Sachs disease characterized by neurological
deterioration between 3 to 6 months of age and progressing to death by
2 to 4 years.
 Visual loss associated with CHERRY-RED SPOT is characterized.

13. Juvenile Tay–Sachs Disease
 Initially seen in children between two and ten years old.
 Patient develop cognitive and motor
skill deterioration, dysarthria, dysphagia, ataxia, and spasticity.
 Death usually occurs between the age of five to fifteen years.

14. Adult/Late-Onset Tay–Sachs Disease
 Symptoms seen in adolescence or early adulthood – include speech and
swallowing difficulties, unsteadiness of gait, spasticity, cognitive decline,
and psychiatric illness, particularly a schizophrenia-like psychosis.

15. Carrier Statistics

16. DIAGNOSIS
 Eye examination (reveals a cherry-red spot in the macula).
 Enzyme analysis of blood or body tissue for hexosaminidase levels (2
pseudo-deficiency alleles and more than 70
pathological mutations have
been identified in the HEX A gene).

17. PRENATAL DIAGNOSIS

19. MANAGEMENT
 Tay-sach disease is currently an incurable disorder, therefore treatment
focuses on the management of symptoms and palliative care.
 Nearly all patients require pharmacological management of their
seizures.
 The psychiatric manifestations of patients with adult-onset are not
usually responsive to antidepressant medication.

20. References
 GeneTests. Medical genetics information resource [database online]. University of Washington, Seattle,
1993-2006. Updated weekly. http://www.genetests.org
 OMIM: Online Mendelian Inheritance in Man. McKusick-Nathans Institute for Genetic Medicine, Johns
Hopkins University, and National Center for Biotechnology Information, National Library of Medicine.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
 Ross LF: Heterozygote carrier testing in high schools abroad: what are the lessons for the U.S.? J Law
Med Ethics 34:753-764, 2006.
IMAGES:
 http://images.slideplayer.com/18/6171172/slides/slide_6.jpg
 http://www.healthandfitnesstalk.com/wp-content/uploads/2013/08/taysachs.gif
 http://myscienceacademy.org/wp-
content/uploads/2012/09/564857_522835031063904_1634463179_n.jpg
 https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcSuK_zd7Zn7XZwBVGqIYHxl_gz6rn-
yoqV3TjP-wauKuDBcM1mA

21. Done By :
Namita Noel