Unit 7 - Introduction to Medical Genetics Flashcards
inherited VS acquired disease
inherited gene complement - mutations may be transmitted from one or both parents (constitutional genome)
-present since birth
acquired gene complement - subset of cells in an individual that arose by clonal propagation from a single mutation in one cell
-arises later in life
what is a syndrome?
set of characteristics which occur together and are assumed to have a common basis
- not all characters occur in all affected individual
- range of variability within a population
what is biochemical genetics?
subspecialty of genetics that deals with diagnosis, treatment, and research of inborn errors of metabolism
what are inborn errors of metabolism?
genetically determined biochemical disorder where a specific enzyme defect produces a metabolic block
- accumulation of substrate
- deficiency of products
alcaptonuria
accumulation of homogentisic acid due to defect in homogentisic acid oxidase in blood damages cartilage, heart, and kidney
what causes albinism?
defect in tyrosine oxidase prevents pigment formation
-can be complete (no pigment in any organ/tissue, plus red eyes) or partial (some organs or tissue have pigment)
what are 3 types of hyperphenylalaninemias?
phenylketonuria
variant PKU
defects in BH4
related to function of phe hydroxylase
when does PKU occur?
AR mutation of phe hydroxylase (PAH) prevents phe –> tyr, causing phe accumulation
- small fraction of phe is converted to phenylpyruvic acid to be detected in urine
- must be treated early and in pregnancy by diet modification
- -even if fetus is non-PKU, mother’s exccess PKU can cross placenta and damage fetus
what is non-PKU hyperphenylalaninemia?
10x increase in phe levels (decrease in phe hydroxylase, but still functional)
- less damaging, may be benign
- may not require special diet
variant PKU
between full PKU and non-PKU hyperphenylalaninemia
-requires diet, but not as restrictive as PKU patients
defect in BH4 metabolism
1-3% of hyperphenylalaninemia patients
- non-mutant phe hydroxylase gene, but mutant DHPR gene (qBH4 –> BH4)
- patients don’t completely respond to PKU diet and develop neurological defects
- thus, supplement with oral BH4 for PAH problem, and L-dopa or OH-trp for sopamine/NE/E and serotonin pathways, respectively
lysosomal storage diseases
recessive due to mutation of lysosomal hydrolytic enzyme that leads to failure of degradation and accumulation of macromolecules in lysosomes
- over 50 known deficiencies, and clinically heterogeneous
- common presentation is progressive degeneration as organelles become larger, so affected organs/tissues increase in mass
how does GM2 gangliosidoses come about?
lysosomal storage disease; 3 genes make 3 PRO that function together
-alpha, beta subunits (come together to form dimer) and activator protein)
Tay Sachs disease?
AR, onset of 3-6 mo, and death in 2-4 years
- deficiency of hexosaminidase A, unable to degrade GM2 ganglioside
- no known treatment, so GM2 builds up in lysosomes and die between 2-4 years
- have cherry red spot in retina of eye
mucopolysaccharidoses symptoms and cause
group of heterogenous disorders
- absence of specific enzyme involves in degradation of glycosaminoglycans
- accumulation of macromolecules in lysosomes
- most are AR, but Hunter syndrome is XLR
- permanent, progressive damage
- short stature, delay, skeletal abnormalities, joint stiffness, thickened skin, heart/liver/spleen damage
- some diseases are more severe than others, are progressive, and worsen over time