PKU, Alpha1 ATD, Tay-Sachs Flashcards
PKU mutation
Usually PAH gene, encodes Phenylalanine Hydroxylase (Phe -> Tyr)
Phenylalanine hydroxylase
Phe -> Tyr … uses O2 and BH4 as cofactor
BH4
Cofactor for Phenylalanine Hydroxylase, 1-3% of PKU disease patients the PAH gene is normal, but they cant recycle this cofactor
Treat PKU?
Low Phenylalanine diet (dietary restriction) Catch early to prevent mental retardation
Timing of PKU test
First tested at Birth and then a few days later at first Peds visit
Screening for PKU
Guthrie Screening = B-2-thienylalanine will inhibit the growth of the bacterium Bacillus subtilis, But if elevated Phenylalanine is present that inhibits Thienylalanine and the bacteria grows.
Do mass spec
Alpha 1- Antitrypsin Deficiency Alleles
M = Normal
Z = Worst (misfold protein) (Glu -> Lys)
S = Moderate (Unstable protein) (Glu -> Val)
Z/Z 10-15% function
S/S 50-60 % Function
Z/S Compound Heterozygote, 30-35% function
Primary target of A1-AT
Elastase, AT deficiency -> TOO MUCH ELASTASE
Leads to the breakdown fo connective tissue in the lungs.. Emphysema
Summary of Alpha 1 Antitrypsin Deficiency
20x increase risk of emphysema (80-90% will develop emphysema
Can also have liver cirrhosis, and increase risk of liver cancer
Tay- Sachs
Muscle weakness, decreased activity, Seizures, Vision/hearing loss, Diminished mental function
CHERRY-RED SPOT on eye
Destroys CNS, Only live about 3-4 yrs
Type of disease is T-S?
Lysosomal Storage Disease,
Unable to store Gmz, builds up in lysosomes in Neurons
T-S Mutation
HexA Gene (Hexosaminidase A needed to metabolize Gmz)
Sandhoff Disease
Same effects and T-S, Affects Both HexA and HexB genes
AB variant of T-S
Both Hex A & B are OK… Defect in Gmx Activarot Protein (Gmz AP)
