BioChem Lab Quiz 9

Gout, Lesh Nylan, Fragile X, Xeroderma

What disease presents with long face, large protuberant ears, pes planus and macroorchidism?

fragile x

What is DNA methylation?

attachment of methyl group to C-G base making a gene SILENT

What gene is silenced in fragile X?

FMR-1

What type of inheritance is fragile x?

x-linked dominant (males affected more)

In fragile x how many repetitions do you have of the code CGG?

200+

FMR-1 mutation/silencing is caused by what?

caused by CGG trinucleotide repeated expansion on FMR-1

What protein is not produced in fragile x?

FMRP

What is function of FMRP (used in fragile x)?

regulate synaptic protein production

What occurs due to FMRP at the synaptic level?

impaired elasticity

dysregulated dendritic protein synthesis

falure of synaptic pruning

immature thin dendtitic spines

How are the synaptic tranmission for fragile x described?

hyperexcitable, poorly tuned, disorganized

Fragile results in what neuropathic symptoms?

learning and memory issues

sensory processing issues

Autistic behaviors

What clinical features does fragile x present with?

intellectual disability

speech delay

autism like-behavior, anxiety ADHD

Premutation in fragile x is as a result of how many repeats of CGG

55-200

What is macroorchidism as presented in fragile x?

enlarged testis

What is the cure to fragile x?

no cure; only types of therapy

What type of diet should not be had for a patient with fragile x?

high carb diet

What does diet help regarding fragile x?

improve metabolic stability → reduce behavioral symptoms

Xeroderma is what type of inheritance?

autosomal recessive

Xeroderma is a malfunction in nucleotide excision repair which leads to what?

dysnfunctional DNA repair

variety of skin/eye abnormalities

A defect in DNA on thymine base due to UV photon is what?

thymine dimer

Steps to fixing thymine dimer?

detection → incision(via endonucleus) → excision (removing) → repair

What does DNA polymerase do?

create new DNA chain

What does DNA ligase do?

attach new DNA chain made

What is the error with xeroderma?

unable to fix defects and mutations (excision)

→ skin hypersensitivity and ROS causing neuronal damage

S/S of xerdoderma on skin:

severe skin burning/blistering

hyper/hypo pigmentation

skin dryness, atrophy

What is big sign of xeroderma in skin?

telangectasias

What type of eye damage is there in xeroderma?

anterior eye damage

What type of neurological s/s is there in xeroderma?

progressive cerebellar and cerebral degeneration

neurocognitive dysfunction, hearing loss

Complications of xeroderma include?

progressive neuronal degeneration

acitinic keratosis → squamous cell carninoma

basal cell carcinoma

What is some treatment of xeroderma for UV protection?

broad-spectrum sunscreen

methylcellulose sunscreen

What other treatments preventative measures are you going to do for a patient with xeroderma?

chemoprevention of skin cancer

Cancer treatment (removals, chemotherapy)

What is the normal life expectancy of a patient with xeroderma?

32

What is the normal life expectancy of a patient with xeroderma with neurodegeneration?

29

What is the normal life expectancy of a patient with xeroderma w/o neurodegeneration?

37

Gout specifically affects which toe?

big toe MTP

What result do you get from synovial fluid laps of gout?

needle-shape negative crystals

Uric acid in the body comes from what? (gout)

purine sources: endogenous, dietary

Which are purines, not sources:

guanine, adenine

What are purines used for?

AMP/GMP

ATP

DNA, RNA

Ribose-5P uses PRPP synthetase to become what?

PRPP → purine

Ribose-5P to eventually purine is called what?

De novo purine synthesis

Degraded purine becomes hypoxanthine and has two pathways, which are?

recycled → via HGPRT

Degraded → via xanthine oxidase to xanthine

Which pathway of purine gets you uric acid and MSU crystals?

degraded

What is the preferred pathway for purine?

recycled

Degraded pathway besides uric acid leads to what?

neutrophils flare (gout)

What protein prevents degrading pathway by stopping xanthine oxidase?

allopurinol

Common misconception about what gout is usually caused by?

red meat

What is the root driver of gout?

hyperuricemia due to underexcretion of urate (renal handling)

What is a major accelerator of gout?

fructose using ATP to degrade

Does hyperinsulinemia cause urate reabsorption to increase?

true

Goal for treatment of gout?

shut down IL-1ß(inflammation)

prevent serum formate formation of crystals

What diet choices should we make for gout?

cut out/decrease fructose

alcohol

sugar

What vitamin should you take for gout to help with flares of gout?

vitamin c

Lesh-Nylan Syndrome is what type of mutation?

x-linked recessive

What does Lesh-Nylan affect?

mutation of HGPRT-1 gene

What increases will we see in Lesh Nylan?

hypoxanthine → xanthine → uric acid

Lesh nylan leads to what?

kidney stones, gout

decrease dopamine and seratonin → decrease cognitive function and self mutilation

motor dysfunction

Lesh nylan treatment is what?

can not fix the gene so treat symptoms

How do we treat the symptoms of Lesh nylan?

allopurinol, calcticine, probenecid for gout

diet → low in purines, fructose, alcohol

dopamine and pyschology referral