Nucleic Acid Diseases Sarge 3-31 Flashcards
Defect in Lesch-Nyhan Syndrome
hypoxanthine phosphoribosyl transferase (HPRT) mutation, where guanine can not be recycled (purine salvage), leading to excessive uric acid formation
Symptoms of Lesch-Nyhan
neurologic problems, facial grimacing, self-mutylation, uric acid deposits in urinary tract and joints
What causes uric acid crystallization
concentration, low pH (made worse by cranberry juice), purines from diet, endogenous purine production
Treatments for Lesch-Nyhan
hydration, restraint devices, drug Allopurinol, a molecule very similar to the natural substrate (hypoxanthine) for xanthine oxidase to inhibit. result =make less uric acid
suicide substrate
allopurinol gets converted to oxypurinol by xanthine oxidase, which is bound more tightly to active site- inhibitory. Other form of suicide substrate is making persistant chemical bond
cause of gout
age, weight, drugs, kidney disease, male, post-menopause
treatments for gout
eat foods low in purines: cheese, eggs, etc.; take drugs controlling for uric acid levels (allopurinol, uricase activators), drink wine
uricostatics
like allopurinol- inhibit production of uric acid
uricolytics
increase breakdown of uric acid in the liver by activating uricase
uricosurics
promote renal excretion of uric acid
Defect in severe combined immunodeficiency (SCID)
Can be caused by several different deficiencies. Most common=Deficiency in adenosine deaminase leading to elevated dATP, which inhibits the conversion of RNA to DNA by ribonucleotide reductase, limiting cells ability to divide- especially T and B cells
Treatment for SCID
injections with enzyme replement therapy PEG-ADA/ Adagen(with effect decreasing over time of use), retroviral gene therapy, bone marrow transplant with sybling stem cell donor
