Lect 1: Intro to Medical Genetics Flashcards Preview

Unit 7 - MCP > Lect 1: Intro to Medical Genetics > Flashcards

Flashcards in Lect 1: Intro to Medical Genetics Deck (33):

patterns of inheritance can be

dominant vs. recessive

autosomal vs. X-linked


inherited vs. acquired dz

inherited gene complement

-mutations may be transmitted from one or both parents


acquired gene complement

a subset of cells in an individual that arose by clonal propagation from a single mutation in one cell


inborn errors of metabolism

genetically determined biochemical disorder in which a specific enzyme produces a metabolic block


What are two mechanisms by which a specific enzyme produces a metabolic block

1. accumulation of substrate which could be toxic

2. deficiency of products



accumulation of homogenistic acids in the blood; damage to cartilage, heart and kidney

--dark urine



can be complete meaning that there is no pigment in any organ or tissue or it can be partial.


Enzyme Defect

If a mutation is present and a substrate cannot be converted to a normal product secondary pathways

may show an increase in activity

The substrate cannot be converted to product 1 or 2, but rather than have a buildup of that substrate, other enzymes activate to convert the substrate to other things (S2, S3, S4)....so that you avoid toxic buildup of substances in the cell.


Deficiency of a Shared Enzyme

a single mutation can affect multiple cellular processes


What are some general clinical features of pts with biochemical disorders

poor growth
mental retardation
problems in general metabolism
neurological problems


1. Hyperphenalaninemias are a group of disorders related to the function of phenylalanine hydroxylase (PAH) which converts phenylalanine to tyrosine.

They include

phenylketonuria (PKU)
variant PKU
defects in tetrahydrobiopterin



due to defect in PAH causing phenylalnine to accumulate in the cells


it is linked to

mental retardation

PHE accumulates and when it does so in nervous tissue cells it damages them causing MR


mom has to be put on a special diet that is low in PHE

If she comes off of it and introduces back into her life, PHE can cross the placenta, damaging the fetus (even tho the baby is not affected with PKU)


Variant PKU and Non-PKU hyperphenylalaninemia

Non-PKU is less damaging and may not require the diet


Another cause of hyperphenylaninemia

is due to mutations along the pathway that make tetrahydrobiopterin (BH4).

-due to locus heterogeneity, mutations in different genes involved in BH4


To make PHE from Tyr you need PAH. PAH requires BH4.

If BH4 is has a metabolism defect it can lead to PHE accumulation

The problem is that BH4 is a cofactor or other enzymes and its absence in other pathways leads to

a deficit in neurotransmitters such as dopamine and serotonin


How do you treat this?

Since PAH is normal, you only need to give 1. oral BH4
2. To normalize neutrotransmitters int he brain, patients require supplementation with the products of the disrupted step such as L-dopa or Trp-OG


What are lysosomal storage dz?

They are caused by mutation of a lysosomal storage enzyme that leads to failure of degradation and the accumulation of macromolecules in lysosomes
include Tay-Sachs


2. GM2 Gangliosidoses

3 dzs due to defect in the pathway


Tay Sachs is due to

a deficiency of hexosiminidase A (hex A) which results in the inability to degrade GM2 gangliosides so they accumulate, especially in the brain.


How do children with Tay-Sachs appear?

they appear normal at birth but hten they begin to decline.


what is a dead giveaway for Tay Sachs

cherry red spot in the retina of the eye....children become progressively worse, losing control of their extremities and usually die btw ages 2 and 4


3. Mucopolysaccharidoses

is due to the absence of enzyme involved in degradation of glycosaminoglycans. if the enzyme is absent or defective the chain will not be degraded.


What substances accumulate in mucopolysaccharidoses



What are the clinical presentations of mucopolysaccharidoses?

permanent, progressive damage

-short stature, delay, skeletal abnormalities and joint stiffness, thickened skin, liver, heart or spleen damage


Treatment of mucopolysaccharidoses?

bone marrow transplant

-enzyme replacemtne therapy

-gene therapy


4. Connective Tissue Disorders

defects in the structural proteins such as collagen and fibrillin


a. OI is caused by

deficiency of type 1 collagen production or defective collagen

-autosomal dominant


b. Ehler-Danlos Syndrome

due to post-translational modification of collagen


What do they present with?

sin fragility, joint hyperflexibility, skin hyperextensibility


c. Marfan Syndrome

due to mutation in the fibrilin gene

-primary defects seen in the skeleton, eyes and heart (aortic dissection)


Marfan patients are

tall, thin with very long fingers. They can have joint laxity and scoliosis and lung problems