Disease of Nucleotide Metabolism

Question 1

Lesh-Nyhan Syndrome

Answer 1

Buildup of uric acid leading to swollen joints and neuro probs like facial grimacing and involuntary writhing
Also get uric acid crystals in kidney and UT

Question 2

Why uric acid crystals in L-N dz?

Answer 2

Because lower pH in these areas and as pH decreases, more acidic and more crystalization
Also more concentrated here

Question 3

What can help reduce formation of uric acid stones?

Answer 3

Hydration

Question 4

L-N behavior

Answer 4

Self-mutilation, facial grimacing, involuntary writhing

Question 5

L-N inheritance

Answer 5

X-linked recessive

Question 6

L-N pathology

Answer 6

Defect in hypoxanthine phosphoribosyl transferase (HPRT)…this normally recycles hypoxanthine and guanine back…without it, xanthine oxidase works overtime to take hypoxanthine to xanthine and xanthine to uric acid

Question 7

L-N blood levels

Answer 7

Increased xanthine, guanine, hypoxanthine, and uric acid

Question 8

L-N treatments

Answer 8

Extra-corporeal shock wave lithotripsy

Allopurinol inhibits xanthine oxidase so less uric acid made (leads to buildup of hypoxanthine)

Question 9

Allopurinol mech

Answer 9

Converted to oxypurinol by xanthine oxidase…won’t leave active site…suicide substrate

Question 10

Gout spiral

Answer 10

Crystal form…WBCs attack…crystals pop cells..cells release proteins…proteins call in more WBCs…proteins lower pH making it possible for more crystals to form

Question 11

Gout risk factors

Answer 11

Men (40-50)
Women after menopause 
Overweight 
Meds
Kidney dz or BP (bc decreased clearnace)
Relatives with gout

Question 12

Alcohol and gout

Answer 12

Beer and hard liquor make it worse

Wine might help?

Question 13

Where can you get purines?

Answer 13

Diet or purine synthesis

Question 14

How can you get rid of pruines?

Answer 14

Renal and gut

Question 15

3 classes of hyperuricemia tx drugs

Answer 15

Uricostatics - inhibt production of uric acid (inhibit xanthine oxidase…allopurinol)
Uricolytics - promote breakdown of uric acid (activate uricase in liver to turn into allantoin)
Uricosurics - promote excretion of uric acid by kidney

Question 16

Why are uricolytics helpful

Answer 16

Breakdown insoluble uric acid into soluble allantoin

Question 17

Gout sufferers should avoid

Answer 17

Yeast, nutes, sardines, meats,

Question 18

ADA def mech

Answer 18

Increased levels of dATP because uric acid pathway is shut off

Question 19

dATP effect

Answer 19

Inhibits ribonucleotide reductase which is needs to make the 4 dNTPs…lack of dNTPs means decreased ability to divide…results in weakened immune system because B and T cells cannot proliferate

Question 20

ADA is one type of

Answer 20

SCID…need germ free environment

Question 21

Txsa for ADA def

Answer 21

PEG-ADA - adagen is ERT…can be given immediately to help control
Gene therapy - modification of stem cells…can cure…must be stabilized
BMT - replace with stem cells..cure…must be stabilized, better in young patients

Question 22

Gene therapy and ADA

Answer 22

Use retrovirus and insert into T cells…then transplant the T cells