Nucleotide Metabolism: Clinical Disorders Flashcards
Discuss the etiology of ARTS syndrome.
🩺 ARTS syndrome stands for Ataxia, Retardation, Tremor and Seizures syndrome. It is caused by mutations in the PRPS1 gene, which is responsible for producing an enzyme called phosphoribosyl pyrophosphate synthetase 1 (PRPP synthetase 1). This disorder is X-linked and is hence more serious in affected males than females.
[Symptoms: profound sensorineural hearing loss, weak muscle tone, imparied muscle coordination, developmental delay, intellectual disability, vision loss due to optic nerve atrophy, peripheral neuropathy]
Discuss the etiology and symptoms of Lesch Nyhan syndrome.
🩺 This is a syndrome caused by severe or complete deficiency of hypoxanthine-guanine phosphoribosyl transferase (HGPRTase), thus the salvage pathway for purine biosynthesis is affected. It is inherited in an X-linked recessive manner hence primarily affects males.
🩺 LNS is characterized by three major hallmarks: neurological dysfunction, cognitive and behavioral disturbances (including self-mutilation), and overproduction of uric acid (hyperuricemia). The latter often results in gout, kidney stones, and bladder stones.
🩺 People with LNS usually cannot walk and generally use a wheelchair.
🩺 Treatment focuses on managing symptoms and improving quality of life.
🩺 Affected people often do not survive past the first or second decade of life due to renal failure.
🩺 [6-minute video]
🩺 [Image 1] [Image 2] [Image 3]
Discuss the etiology of Gout.
🩺 This is a type of arthritis that causes intense pain, swelling, and stiffness in a joint; classically, it affects the joint in the big toe.
🩺 It is caused by elevated levels of uric acid and deposition of sodium urate crystals in the joints and kidneys. It may be caused by genetic deficiency in some enzymes in the purine biosynthetic pathway.
🩺 [6-minute video]
[Diagram] [Image 1] [Image 2] [Image 3]
What are three inherited defects that may lead to early development of severe hyperuricemia and gout?
(1) Glucose-6-phosphate dehydrogenase [G6PD] deficiency
(2) Severe and partial hypoxanthine-guanine phosphoribosyl transferase (HGPRase) deficiency
(3) phosphoribosyl-1’-pyrophosphate synthetase (PRPP synthetase) activity
Discuss risk factors associated with Gout.
(1) Age and Gender: Men produce more uric acid than women, though women’s levels of uric acid approach those of men after menopause.
(2) Genetics: A family history of gout increases the likelihood of the condition developing.
(3) Lifestyle choices: Alcohol consumption interferes with the removal of uric acid from the body. Eating a high-purine diet also increases the amount of uric acid in the body.
(4) Lead exposure: Chronic lead exposure has been linked to some cases of gout.
(5) Medications: Certain medications can increase the levels of uric acid in the body; these include some diuretics and drugs containing salicylate.
(6) Weight: Being overweight increases the risk of gout as there is more turnover of body tissue, which means more production of uric acid as a metabolic waste product. Higher levels of body fat also increase levels of systemic inflammation as fat cells produce pro-inflammatory cytokines.
(7) Recent trauma or surgery: increases risk
(8) Other health problems: renal insufficiency and other kidney problems can reduce the body’s ability to efficiently remove waste products, leading to elevated uric acid levels.
Discuss treatment and prevention of Gout.
Treatment
🩺 Allupurinol: It is a hypoxanthine analog and binds tightly to xanthine oxidase, thereby inhibiting the enzyme’s activity. As a result, products of purine catabolism i.e. xanthine and hypoxanthine, which are more soluble are excreted and are less likely to form crystals than uric acid.
🩺 Other medications e.g. NSAIDs, colchicine and corticosteroids may be administered to reduce pain and inflammation.
Prevention
🩺 Diet control: Avoiding foods high in purines, such as red meat, organ meats, and certain seafoods. Limit alcohol intake, especially beer, and avoid sugary beverages.
🩺 Adequate hydration
🩺 Weight management
