Intro To Medical Genetics Flashcards
Mutations occur at
cytogenetic or molecular level
A mutation is
Permanent, heritable change in sequence in DNA
Mutations can be
Positive, negative, or neutral
A syndrome is
a disorder with a set of characteristics that occur together and assumed to have a common basis.
With syndromes there is a
range of variability, not all people have all characters
Inborn errors of metabolism are
genetically determined biochemical disorders in which a specific enzyme defect produces metabolic block
Inborn errors of metabolism are characterized by
accumulation of substrate and deficiency of products
alcaptonuria
accumulation of homogentistic acid in the blood; damage to cartilage
albinism is caused by a mutation in
tyrosine oxidase
albinism can be
complete: no pigment in any organ or tissue
or incomplete: some organs or tissues have pigment
When a substrate cannot be converted to normal product ___ can increase in activity. Why?
secondary pathways; can be salvage pathways to prevent build up of toxic substances
Why can it be bad that enzymes may partake in more than one pathway?
a single deleterious mutation in such an enzyme can affect many processes negatively
What are the characteristics of the inborn errors of metabolism?
- single enzyme defect
- recessive
- many recognized disorders
- challenge to detect the particular pathway and substance involved
- use biochem and genetics to make a diagnosis
What are the common features of patients with biochemical disorders?
poor growth
mental retardation
problems in general metabolism
neurological problems
What information can hint to biochemical dysfunction?
clinical picture, onset of MR over time, other affected siblings, unexplained infant deaths
what are the hyperphenlalaninemias
phenylketonuria, variant PKU, and defects in BH4
all involve disorders in the function of phenylalanine hydroxylase
phenylketonuria
PAH can’t convert Phe to Tyr, and Phe builds up
AR
1/10k births
causes mental retardation
treated by diet modification ( low Phe diet) early in life and especially during pregnancy
why do pregnant women with PKU need to be careful?
Excess Phe is teratogenic, even if the fetus doesn’t have PKU
Non-PKU hyperphenylalaninemia
~10 fold increase in Phe levels
less damaging, may be benign
may not require special diet
Variant PKU
between full PKU and non-PKU hyperphenylalaninemia; requires a diet, but not as restrictive as PKU patients
BH4 mutations are an example of
locus heterogenity, when mutations in different genes lead to the same clinical phenotype
How is BH4 treated?
oral BH4 and supplementation with neurotransmitters that are lacking
Why is a mutation in BH4 more serious?
- may not completely respond to PKU diet
- develop neuro deficits
- cofactor for enzymes needed to make dopamine and serotonin
Describe the lysosomal storage diseases
- recessive
- muation in lysosomal hydrolytic enzyme–>failure to degrade
- accumulation of macromolecules
- clinically heterogeneous
- presents with progressive degeneration
