Hypouricemia
Encyclopedia
Hypouricemia is a level of uric acid
Uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...

 in blood serum
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...

 that is below normal. In humans, the normal range of this blood component has a lower threshold set variously in the range of 2 mg/dL to 4 mg/dL, while the upper threshold is 530 micromol/L (6 mg/dL) for women and 619 micromol/L (7 mg/dL) for men. Hypouricemia usually is benign and sometimes is a sign
Medical sign
A medical sign is an objective indication of some medical fact or characteristic that may be detected by a physician during a physical examination of a patient....

 of a medical condition.

Causes

Hypouricemia is not a medical condition itself (i.e., it is benign), but it is a useful medical sign. Usually hypouricemia is due to drugs and toxic agents, sometimes it is due to diet or genetics, and rarely it is due to an underlying medical condition. When one of these causal medical conditions is present, hypouricemia is a common sign.

Medication

The majority of drugs that contribute to hypouricemia are uricosuric
Uricosuric
Uricosuric medications are substances that increase the excretion of uric acid in the urine, thus reducing the concentration of uric acid in blood plasma. In general, this effect is achieved by action on the proximal tubule...

s (drugs that increase the excretion of uric acid from the blood into the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...

). Others include drugs that reduce the production of uric acid: xanthine oxidase inhibitor
Xanthine oxidase inhibitor
A xanthine oxidase inhibitor is any substance that inhibits the activity of xanthine oxidase, an enzyme involved in purine metabolism. In humans, inhibition of xanthine oxidase reduces the production of uric acid, and several medications that inhibit xanthine oxidase are indicated for treatment of...

s, urate oxidase
Urate oxidase
The enzyme urate oxidase , or uricase or factor-independent urate hydroxylase, catalyzes the oxidation of uric acid to 5-hydroxyisourate:-Structure:...

 (rasburicase
Rasburicase
Rasburicase is a recombinant version of a urate oxidase enzyme that occurs in many mammals but not in humans.-Uses:Rasburicase is approved for use by the U.S...

), and sevelamer
Sevelamer
Sevelamer is a phosphate binding drug used to prevent hyperphosphatemia in patients with chronic renal failure. When taken with meals, it binds to dietary phosphate and prevents its absorption...

.

Diet

Hypouricemia is common in vegetarians due to the low purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....

 content of most vegetarian diets. Vegetarian diet has been found to result in mean serum uric acid values as low as 239 µmol
Mole (unit)
The mole is a unit of measurement used in chemistry to express amounts of a chemical substance, defined as an amount of a substance that contains as many elementary entities as there are atoms in 12 grams of pure carbon-12 , the isotope of carbon with atomic weight 12. This corresponds to a value...

/L
Litér
- External links :*...

 (2.7 mg/dL). While a vegetarian diet is typically seen as beneficial with respect to conditions such as gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...

, care should be taken to avoid associated health conditions.

Transient hypouricemia sometimes is produced by total parenteral nutrition
Total parenteral nutrition
Parenteral nutrition is feeding a person intravenously, bypassing the usual process of eating and digestion. The person receives nutritional formulae that contain nutrients such as glucose, amino acids, lipids and added vitamins and dietary minerals...

. Paradoxically, total parenteral nutrition may produce hypouricemia followed shortly by acute gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...

, a condition normally associated with hyperuricemia
Hyperuricemia
Hyperuricemia is a level of uric acid in the blood that is abnormally high. In humans, the upper end of the normal range is 360 µmol/L for women and 400 µmol/L for men.-Causes:...

. The reasons for this are unclear.

Genetics

Genetic mutations known to cause hypouricemia are of two kinds: mutations causing xanthine oxidase
Xanthine oxidase
Xanthine oxidase Xanthine oxidase Xanthine oxidase (XO (sometimes 'XAO'), a form of xanthine oxidoreductase that generates reactive oxygen species. Is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid...

 deficiency, which reduces the production of uric acid; and mutations causing abnormal kidney function that increases the excretion of uric acid. Collectively known as familial renal hypouricemia, these latter mutations are of two types, involving defects of presecretory and postsecretory reabsorption.

A genetic mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

 in Dalmatian dogs
Dalmatian (dog)
The Dalmatian is a breed of dog whose roots are often said to trace back to Dalmatia, a region of Croatia where the first illustrations of the dog have been found. The Dalmatian is noted for its unique black- or brown-spotted coat and was mainly used as a carriage dog in its early days...

 causes hypouricemia due to a kidney defect that interferes with reabsorption of uric acid. A similar mutation has been reported in a human brother and sister.

In humans, loss-of-function mutations in the gene URAT1 are associated with presecretory reabsorption defects.

Medical conditions

Medical conditions that can cause hypouricemia include:
  • Fanconi syndrome
    Fanconi syndrome
    Falconi syndrome is a disease of the proximal renal tubules of the kidney in which glucose, amino acids, uric acid, phosphate and bicarbonate are passed into the urine, instead of being reabsorbed. Fanconi syndrome affects the proximal tubule, which is the first part of the tubule to process fluid...

  • Hyperthyroidism
    Hyperthyroidism
    Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...

  • Multiple Sclerosis
    Multiple sclerosis
    Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...

  • Myeloma
  • Nephritis
    Nephritis
    Nephritis is inflammation of the nephrons in the kidneys. The word "nephritis" was imported from Latin, which took it from Greek: νεφρίτιδα. The word comes from the Greek νεφρός - nephro- meaning "of the kidney" and -itis meaning "inflammation"....

  • Wilson's disease
    Wilson's disease
    Wilson's disease or hepatolenticular degeneration is an autosomal recessive genetic disorder in which copper accumulates in tissues; this manifests as neurological or psychiatric symptoms and liver disease...


Prevalence

In one study, hypouricemia was found in 4.8% of hospitalized women and 6.5% of hospitalized men. (The definition was less than 0.14 mmol l-1 for women and less than 0.20 mmol l-1 in men.)

Diagnosis

Uric acid clearance should also be performed, increase in clearance points to proximal tubular defects in the kidney, normal or reduced clearance points to a defect in xanthine oxidase.

Treatment

Idiopathic
Idiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...

 hypouricemia usually requires no treatment. In some cases, hypouricemia is a medical sign
Medical sign
A medical sign is an objective indication of some medical fact or characteristic that may be detected by a physician during a physical examination of a patient....

 of an underlying condition that does require treatment. For example, if hypouricemia reflects high excretion of uric acid into the urine (hyperuricosuria
Hyperuricosuria
Hyperuricosuria is a medical term referring to the presence of excessive amounts of uric acid in the urine. Notable direct causes of hyperuricosuria are dissolution of uric acid crystals in the kidneys or urinary bladder, and hyperuricemia...

) with its risk of uric acid nephrolithiasis, the hyperuricosuria may require treatment.

Drugs and dietary supplements that may be helpful

  • Inositol
    Inositol
    Inositol or cyclohexane-1,2,3,4,5,6-hexol is a chemical compound with formula 6126 or 6, a sixfold alcohol of cyclohexane. It exists in nine possible stereoisomers, of which the most prominent form, widely occurring in nature, is cis-1,2,3,5-trans-4,6-cyclohexanehexol, or myo-inositol...

  • Antiuricosurics

Complications

Although normally benign, idiopathic
Idiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...

 renal hypouricemia may increase the risk of exercise-induced acute renal failure
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...

.
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