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
treatment for mucopolysaccharidoses
- bone marrow transplantation
- enzyme replacement therapy
- gene therapy
osteogenesis imperfecta symptoms and cause
due to mutations in type I collagen with either reduced collagen production or defective collagen
- 4 major classes that range from mild to lethal, all AD
- -I - mildest; reduced collagen production (collagen made in half the normal quantity, causing brittle bones)
- -II - perinatal lethal
- -III - between II and IV
- -IV - mild to moderate bone deformity and fracturing
- major character is brittle bones and skeletal deformities
Ehler-Danlos syndrome
error in post-translational modification of collagen (primarily COL5A or COL3A genes) with multiple subtypes (AD, AR, and XLR)
-have fragile skin, joint hypermobility, and skin hyperextensibility
Marfan syndrome symptoms and causes
connective tissue disorder of fibrillin gene
- primary targets are skeleton, heart, lungs, and eyes
- tall and thin, with very long fingers, joint laxity, and scoliosis
- lung problems cause pneumothorax
- dislocation of lens or myopia are common findings
- cataracts, glaucoma, and retinal detachment are additional problems
- heart issues include mitral valve prolapse, dilatation, and dissection of aorta (common death cause is rupture of thin aorta)
Marfan syndrome treatment
no known cure, but effective management
- know limits, limit stress
- surgical repair of aorta is possible
- orthopedic braces and devices help skeletal issues, and there are well-established management programs for eye problems
