1-20 21 Autosomal Recessive Disorder

Question 1

Macular Cherry Red Spot

Answer 1

where best sharpest color vision is in eye, in tay sachs eye this spot appears and is a sign of abnormal eye layers and thinning

Question 2

Classic Tay-Sachs Disease phenotype

Answer 2

• normal dev 3-5 months
• gradual slowing of progress until loss of milestones
• hyperacusis, easily startled
• progressive weakness and hypotonia
• decrease in visual attentiveness, abnormal eye movements

by 8-10 months: decrease in awareness/activity, seizures, vegetative, deathy by age 5

Question 3

Tay sachs genetics

Answer 3

autosomal recessive, gene: HEXA

β-hexosaminidase A helps to degrade a lipid called GM2 ganglioside

allowing excessive accumulation of the GM2 ganglioside in neurons. The progressive neurodegeneration seen in the varied forms of Tay-Sachs depends upon the speed and degree of GM2 ganglioside accumulation

much lower activity of serum hexosaminidase levels normal BUT %A hexosaminidase 10 fold lower

Question 4

Genetic testing of Jewish folk

Answer 4

test for Tay sachs disease variant, if both partners in a couple carriers, council

this testing has dramatically decreased incidence of tay sachs in US/canada

Question 5

Mucopolysaccharidosis I

Answer 5

mutations in ability to breakdown glycosaminoglycans, autosomal recessive

joint contractures/stifness
enlarged liver and spleen
coarse facies
corneal clouding
dysostosis multiplex
*corneal opacification*

urine test detects inappropriate amounts of glycosaminoglycans

Different subtypes of MPS have deficiencies in different steps of glycoprotein/phosphorylation/breakdown

compound heterozygosity

Question 6

allelic heterogeneity:

loci heterogeneity:

Answer 6

same gene spot, different variations, same disorders

different genes, different spots, same disorders

Question 7

propionyl CoA carboxylase deficiency

Answer 7

unable to transform propionyl coa —–>methylmalonyl coA (TCA) so builds up intermediates (propionic acid, lactate, methylcitrate) which are problematic

treatment: recognized that all carboxylases require biotin to deliver carbon
- pathway: free biotin is intook from diet, associates with apocaroxylases, holocardozylase synthetase, holocarboxylase active to do job!, undergo proleolytic degredation and recycle biotin-lysine, biotinidase removes biotin for recycling to apoenzymes again

Question 8

galactose build up

Answer 8

galactose -> galactose1phos (toxic) via TRANSFERASE (damaged)-> UDP-galactose

results in build up of Gala1phos therfore builds up galactose therefore builds up galactitol therefore cataracts

Question 9

coumpound heterozygosity

Answer 9

having two or more heterogeneous recessive alleles at a particular locus that can cause genetic disease in a heterozygous state; that is, an organism is a compound heterozygote when it has two recessive alleles for the same gene, but with those two alleles being different from each other (for example, both alleles might be mutated but at different locations). Compound heterozygosity reflects the diversity of the mutation base for many autosomal recessive genetic disorders; mutations in most disease-causing genes have arisen many times. This means that many cases of disease arise in individuals who have two unrelated alleles, who technically are heterozygotes, but both the alleles are defective.