Flashcards in Autosomal Recessive Deck (55)
Chance of unaffected sibling being carrier?
Location of majority of mutant allele?
Hidden in carriers
For an affected child of an AR disorder, the more rare the disease, the higher the chance of?
High phenylalanine in blood
High phenylalanine metabolites in urine
Hyperactivity and epilepsy
Mental retardation and microcephaly
PKU biochemical defects?
98% Defect in PAH (phenylalanine hydroxylase)
1-2% defect in BH4 synthesis/recycle (PAH cofactor also involved in serotonin and dopamine biosynthesis)
PKU and mutant alleles?
High allelic heterogeneity
Varied phenotype severity
PKU: Newborn screening
Mass spectrometry to look at absolute phenylalanine level as well as phenylalanine/tyrosine ratio
PKU: Newborn screening timing?
Wait a moment because brand new bambino can retain mama enzyme
PKU Maternal Effect
PKU women who are off low-phenylalanine diet in pregnancy have markedly increased risk of miscarriage or congenital malformation and mental retardation of babies
PKU Maternal Effect Prevention
Maintain low Phe diet throughout child bearing years
Low Phe diet
Neutral a.a. supplement (BBB)
ATD (Alpha1 antitrypsin deficiency)
Deficiency in alpha1-antitrypsin (SERPINA1, AAT) a protease inhibitor - (of elastase)
ATD - more common in?
carrier frequency - 4%
ATD diagnostic issue?
Increased risk of ?
Liver cirrhosis -> cancer
ATD and ecogenetics?
Earlier and more severe in smoker
The phenomenon where genes and lifestyle influence phenotype, such as early and more severe ATD symptoms in smokers is known as?
ATD biochemical defects
Deficiency in Alpha-1 antitrypsin
What is alpha1-antitrypsin?
a protease (elastase) inhibitor
What is elastase?
An enzyme released by activated neurtrophils at the airway, destroying elastin in connective tissues
ATD patients have imbalance of?
Elastase and SERPINA1
ATD is caused by?
Mutation in alpha1-AT (SERPINA1) gene
Where is alpha1-AT produced?
Where is alpha1-AT transported?
to the lungs via blood from the liver
How many common alleles encode functional alpha1AT
Three common M alleles
What are the two most common mutant alleles that cause ATD?
Z allele (Glu342Lys) - most common mutant allele
S allele (Glu264Val)
Allelic heterogeneity in PKU and ATD
ATD has relatively little alleleic heterogeneity, with two common, Z and S, mutant alleles causing phenotype - unlike PKU which can have many mutant alleles