Glossary

This list of specialist terms is based on the glossary provided in the book Gout: Answers at your Fingertips, 2013, with the kind permission of the publishers. http://www.classhealth.co.uk/books/gout-answers-at-your-fingertips-94

Words in italic in the definitions are also defined in this list. NB British spelling is used throughout.

acute

A word meaning ‘sharp’ -- thus it describes a condition where the symptoms appear rapidly and are severe or painful. In gout, the acute attack has a brief duration compared with chronic (long-term) accumulation of uric acid.

ADA

Adenosine deaminase – an enzyme that recycles purines within the cell. Deficiency of the enzyme prevents development of both T- and B-lymphocytes and thus causes one form of SCID. Several patients have successfully been treated with gene therapy, which inserts a healthy form of the ADA gene into the cells.

ADSL or ASA

Abbreviation for an enzyme involved in making purines in the cell: patients with defects are very rare. ADSL deficiency may give rise to varying extents of epilepsy, muscle wasting, movement disorders and autism.

adenine/adenosine

Adenine is one of the nitrogen-containing bases, or purines, that occur in the nucleic acids (DNA and RNA) found in nearly all cells. Adenosine is a related chemical but also containing a sugar molecule (See also ATP.)

addiction

Physical dependence on a drug that is taken regularly -- leading to unpleasant ‘withdrawal symptoms’ when the drug is stopped. This term is also often used when the dependence is psychological. In each case the drug should be withdrawn gradually.

allergic reaction

An over-reaction of the body’s immune system to a foreign particle or chemical. When the body encounters the trigger again, its reactions can range from mild symptoms resembling hay-fever to severe inflammation, dermatitis and shock.

allogeneic stem-cell transplantation

A procedure in which a person receives blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical, donor. This is often a sister or brother, but could be an unrelated donor. The new cells provide the patient with an enzyme (for example thymidine phosphorylase) which is otherwise missing from their own blood cells.

allopurinol

A drug, frequently prescribed for gout, that acts to reduce the levels of uric acid formed from turnover of purines in the body. It inhibits the enzyme xanthine oxidase. The tablets may be generic allopurinol, or provided under the trade names Hamarin or Zyloric.

ampicillin

An antibiotic, one of the penicillin group. Ampicillin is known to have a uricosuric effect, but can interfere with the action of some urate-lowering treatment.

analgesic

A pain-killing drug, such as aspirin, paracetamol, NSAIDs, narcotics.

antibiotic

A drug that can kill bacteria without harming the patient (unless he or she is allergic to it); for example, penicillins, tetracyclines, aminoglycosides, cephalosporins, streptomycin.

anti-inflammatory drugs

Drugs that react against various causes of inflammation. For gout, the corticosteroid drugs and colchicine are useful anti-inflammatories. NSAIDs also act as painkillers where the inflammation is the cause of the pain, by inhibiting the cyclo-oxygenase enzymes (COX-1 and COX-2), but are now being used less than previously because of long-term side effects.

APRT

Adenosine phosphoribosyl transferase, an enzyme that carries out a reaction to recycle purine nucleotides in the body. Deficiency of APRT in humans may lead to kidney stones, formed of salts and insoluble chemicals related to adenine.

arthritis

Inflammation of one or more joints, resulting in pain, heat, swelling and redness over the affected joint, the movement of which will be restricted. There are many types of arthritis, including rheumatoid arthritis, ankylosing spondylitis, infectious (or septic) or reactive arthritis, degenerative (‘wear and tear’) conditions such as osteoarthritis, and metabolic forms of arthritis such as gout.

ATP

Adenosine triphosphate, a purine-containing compound that is needed in all cells to store chemical energy for the conversion of small molecules into other material, and for the contraction of muscle. Over half the uric acid excreted through the kidneys is derived from ATP.

autosomal recessive

A mode of inheritance in which disease occurs only if both parents have passed on a faulty copy of the gene encoding an enzyme. Since the gene is found on one of the autosomes – not the X or Y chromosomes – the enzyme activity may be partially deficient in half of the offspring of either sex, and completely absent in one-quarter of the offspring of the parents carrying the defective versions of the gene. See MNGIE.

BMI

Body mass index, calculated from height and weight, gives an indication of long-term risk of diseases connected with excess body fat.

caffeine

A stimulant and mild diuretic found in coffee, tea and some over-the-counter preparations sold as painkillers and for the relief of cold symptoms. Some canned soft drinks contain caffeine: e.g. Coca-Cola, Pepsi, Lucozade, Red Bull. If it is present, caffeine will always be noted on the label of packaged drinks and painkillers.

calorie-controlled diet

An effective way to lose weight, provided it is accompanied by will-power and increased physical activity. The simplest way to cut calories is to eat smaller portions of your regular diet but, because fatty foods contribute calories in the most concentrated form, cutting fats will be most effective. Low-carbohydrate diets are now being recommended more frequently, because they help to control the symptoms of Type 2 diabetes, and a low-carbohydrate diet tends to be less ‘hungry’.

CDPPT

Abbreviation for an enzyme involved in the use of pyrimidines in the cell: defects may give rise to haemolytic anaemia.

cerebral palsy

A disorder, with a variety of causes, appearing before the age of three years and affecting voluntary movements (walking, talking, manipulation). Lesch-Nyhan disease (LND) is an inherited form of cerebral palsy caused by the defect in HPRT activity.

chemotherapy

The use of chemicals to cure or to manage a disease. Usually the term refers to treatment of cancer with drugs to kill cancer cells, contrasting with radiotherapy which uses x-rays.

choreo-athetosis

A disorder of movement in which the person weaves irregularly and sways like a dancer. The movements are involuntary. See also cerebral palsy.

chronic

A term to describe a condition with a gradual onset and slow changes over a long time. Such a condition may or may not be severe or life-threatening. In gout, the chronic condition may also have acute episodes with broadly the same cause.

chronic tophaceous gout

Long-standing gout in which tophi (singular tophus) are deposited in and around joints. In some people, the tophi are the principal symptom, and there is little arthritic pain.

colchicine

A drug derived from the autumn crocus plant, colchicum. It is effective in relieving the pain of gouty arthritis attacks.

corticosteroid

Naturally occurring chemicals (hormones) produced by the adrenal glands, or synthetic drugs with similar chemical structures and effects. The drugs are powerful anti-inflammatory agents. (Also called ‘steroids’, which should not be confused with anabolic steroids sometimes used illegally by athletes to build up their muscular strength.)

COX-2 inhibitors

A class of NSAIDs which inhibit the action of the enzyme cyclo-oxygenase-2 and thus relieve pain caused by inflammation. Their advantage over other (COX-1) NSAIDs is the reduced effect on the stomach, lowering the risk of gastric ulcers or bleeding in the stomach. However they can cause serious cardiovascular problems. The National Institute for Health and Clinical Excellence (NICE) recommends etoricoxib for gout pain.

CVS

Chorionic villus sampling. After the ninth week of pregnancy, a tiny sample of cells is removed from the part of the placenta provided by the fetus. The cells are studied to determine if there are any abnormalities in the chromosomes or in certain enzymes, which would imply a disorder in the developing baby.

degenerative diseases

Conditions occurring usually in later life, partly caused by wear and tear in the body, such as osteoarthritis, Type 2 diabetes and hypertension (high blood pressure).

DHPA and DHPD

Abbreviations for two enzymes that remove the final products from the breakdown of pyrimidines in the body. Some serious neurological problems may result when either of these enzymes is defective.

diabetes

This term usually refers to diabetes mellitus, of which there are two main types. Type 1 diabetes occurs in childhood or adolescence in people who cannot make enough of the hormone insulin to control the body’s use of sugars and carbohydrate food. The condition is severe but it can be controlled by injections of insulin. Type 2 diabetes typically occurs after the age of 40 in people whose body responds inadequately to insulin. A similar condition, maturity-onset diabetes in the young (MODY) is now increasingly seen in children and teenagers, especially those who are obese. Drugs or insulin may be given, but emphasis is also placed on a healthy diet, with weight reduction if appropriate.

diet

This word refers to everything that you eat and drink, not merely to a specialised weight-loss regimen. If your regular diet provides too much sugar and fat, you may be recommended to cut calories or to eat smaller portions. See also low-purine diet.

diuretics

Drugs that promote the excretion of salts and water from the kidney, and so are often referred to as ‘water tablets’. They are usually prescribed to reduce oedema (puffiness) around the ankles and lower legs that may be caused by any of several disorders. When levels of uric acid in the kidney are high, some diuretics (e.g. thiazides such as bendrofluazide) are known to interfere with its excretion into the urine, resulting in high levels in the blood.

DNA

Deoxyribonucleic acid, a giant molecule in the nucleus of all cells. DNA is especially important in cells that are dividing, because it contains the genetic information which enables cells to carry out their functions, in particular to divide and produce another cell of identical genetic composition, and to manufacture enzymes and structural components of the cells. DNA, in the form of chromosomes, is transferred to the cells that will become eggs and sperm, and hence the information is transmitted to the next generation. A tiny proportion of the genome (37 genes) is found in mitochondria.

Down Syndrome

(formerly Down’s syndrome) A congenital condition in which all or some of the cells in the body have an extra copy of chromosome 21; in some people only part of chromosome 21 is duplicated. With either type of genetic variation, children experience similar effects from the syndrome, which may include learning disability, deafness, facial characteristics and hyperuricaemia.

drug interaction

Two or more drugs taken together can cause a loss or increase in their potency, or may alter the period during which one of the drugs is active. Some drug interactions alter the speed or efficiency of natural processes, such as the excretion of uric acid from the kidneys.

enzymes

Protein molecules in all cells of our body, and in our digestive system that cause chemical reactions to occur. Because each enzyme has a very specific structure, related to the reaction it performs, drugs can be designed to knock out the action of one enzyme. This is the basis of allopurinol’s effect on the production of uric acid.

FJGN or FJHN

(Familial juvenile gouty/hyperuricaemic nephropathy). A condition characterised by kidney failure in early life accompanied by high levels of uric acid in the blood, which often results in tophaceous gout.

fructose

Fructose or ‘fruit sugar’ is a monosaccharide (simple sugar) that is found naturally in fruits. It constitutes half of the molecule of the disaccharide sucrose (cane sugar) and thus is found in all sweet foods. In recent years, the industrial use in the West of FRCS (fructose-rich corn syrup) in soft drinks and processed food such as confectionery and baked goods has occurred alongside an increase in obesity, diabetes and hypertension. It has also been found that fructose contributes to an increased risk of gout.

gastric ulcer

An open sore in the lining of the stomach, which may fail to heal unless treated. The naturally acid juices in the stomach, digestive enzymes and bile, may act on the mucous lining of the stomach to form ulcers, but taking NSAIDs or corticosteroids can increase the risk.

gene therapy

A process in which a disorder arising from a defective enzyme step is treated by inserting the ‘correct’ gene encoding the enzyme into the patient’s cells. Typically, the new gene is introduced within a harmless virus; the virus DNA and gene enter the nucleus of the cells; the new gene directs the production of the normal enzyme. At present, only certain tissues or blood cells can be treated in this way.

genetic/genetic code

Referring to the inheritance of characteristics from parents. The genetic code is a chemical means of ‘reading’ the information from the DNA of the chromosomes. A similar code is used in the messenger molecules (messenger RNA) which are used in each cell of the body to make the proteins that will contribute to the eventual shape and function of the body. Reports in newspapers and TV often refer to advances made by investigating a patient’s ‘genetic code’: in this case they usually mean the complete ‘message’, or genome, which contains instructions for the growth and development of the body.

genetic counselling

Advice given to parents who wish to consider the likelihood that an inherited disorder will affect their children. Usually parents will know that one of them carries the faulty gene, or they may already have one child with such a disorder and will need to think about the options for diagnosing an affected child before birth (see prenatal diagnosis), and/or for terminating the pregnancy.

genome

The genetic information contained in every cell: this one word describes the chromosomes, containing genes, which in turn are made from DNA. Genes encode the information for making proteins and other molecules at the correct time and in the correct place in living cells.

gout

A disease resulting from the accumulation of uric acid in the blood and the formation of crystals of monosodium urate in the joints. The acute phase -- gouty arthritis -- is a painful attack of arthritis, usually in the big toe, with a very rapid onset. Chronic gout may include the deposition of urate salts as tophi in the skin, bone and cartilage, and high levels of uric acid may damage the kidneys. With modern drug treatment and a low-purine diet, primary gout can be well controlled. Rare defects in the metabolism of purines, or a familial nephropathy, may also be associated with gout symptoms. (See also primary gout and secondary gout.)

guanine/guanosine

Guanine is one of the nitrogen-containing bases, or purines, that occurs in the nucleic acids DNA and RNA in all cells. Guanosine is a related chemical, found in beer.

HPRT or HPRTase or HGPRTase

Abbreviations for the enzyme hypoxanthine-guanine phosphoribosyltransferase, which carries out a crucial step in the recycling of purines that result from daily turnover of purines in the body. Complete lack of HPRT results in Lesch-Nyhan disease (LND), while partial deficiency of the activity will lead to the symptoms of LND variant or KSS. The gene for HPRT is carried on the X chromosome, so these conditions are usually only seen in boys.

HRT

Hormone replacement therapy: usually refers to female steroid hormones given to women who have passed the menopause.

hypertension

High blood pressure. There are many causes, including narrowing of the renal artery, and many complications, including renal failure. Combinations of drugs (anti-hypertensives) may be used to control the blood pressure, and weight loss may also be advised.

hyperuricaemia

An abnormally high level of uric acid or urate salts in the blood. This may be caused by re-absorption of uric acid by inefficient kidneys, or may result from high levels of uric acid as purines are metabolised for excretion.

hyperuricosuria/hyperuricuria

An abnormally high level of uric acid in the urine. It may be caused by efficient excretion of uric acid, made from a high concentration of purines in the diet or from our cells. The concentration of uric acid in the blood should also be measured for comparison.

IMPDH

Inosine monophosphate dehydrogenase: enzyme that carries out a crucial step in the biosynthesis of purines. Two different forms of the enzyme are found in the body, encoded by two distinct genes. When one form is inhibited by a drug such as mycophenolate mofetil, the immune system is suppressed.

Kelley--Seegmiller syndrome (KSS)

A metabolic disorder resulting in over-production of purines, for the same reason as Lesch--Nyhan disease. In KSS, the enzyme HPRT is defective rather than completely absent, so affected boys do not have any of the problems in the central nervous system as found in LND. The first indication that a boy has KSS may be renal failure after an infection, dehydration or the use of antibiotics, all of which impede the excretion of uric acid from the kidneys. The principal long-term concern is gouty arthritis, which can be treated with allopurinol. Diet may also be used for long-term management of the hyperuricaemia (see Chapter5).

kidney stones (renal calculi)

Hard masses formed in the kidney tubules from insoluble material that becomes concentrated during the excretion processes taking place in the kidneys. The most common kidney stones are composed of calcium salts. Uric acid stones may be formed when hyperuricosuria has been present for several years. Stones may cause pain, but often there are no symptoms until the kidney tubules become blocked. If the flow of urine is obstructed, there is a danger of infection in the urinary tract and the kidney(s).

Lesch--Nyhan Disease/syndrome (LND/LNS)

An inherited metabolic disorder resulting in over-production of purines, and thus in high levels of uric acid. The gene coding for the enzyme HPRT is inherited on the X chromosome, and, because boys have only one X chromosome, the condition affects boys who only have a defective copy of the gene on their single X chromosome. Their mother and sisters may either lack one copy or carry one defective copy of the gene with no apparent ill-effect since they also have a second, normal X chromosome. Very rarely, girls may be affected if their cells express the faulty X chromosome. Affected children have gout, increased muscular activity, poor co-ordination and involuntary, jerky movements, and a distressing compulsion to bite or scratch themselves (self-mutilation). The gout can be controlled with allopurinol.

LND variants

Boys with an LND variant have milder symptoms in the nervous system but the same over-production of uric acid.

low-purine diet

A diet that restricts the intake of red meat, organ meat, seafood, wheat germ and yeast extracts. Gout sufferers usually attempt to eliminate purine-rich food from their diets, but it is now known that other foods and drinks, not particularly rich in purines, can also influence the accumulation of urate and lead to gouty attacks. A diet that is low in purines will also be low in pyrimidines.

lithaemia

Another term for hyperuricaemia.

lithiasis

Stones (which may be composed of various insoluble compounds, including oxalic acid and uric acid, singly or together) deposited in the kidneys, urinary tract, gall-bladder, etc.

metabolic/metabolism

Concerning the reactions in the body that convert food and other chemicals to provide energy and raw materials in the body’s cells. Also includes the reactions that re-use or excrete substances including drugs.

metabolic disease

Symptoms arising from derangements in the normal series of enzyme reactions that convert molecules inside the body either to produce energy, or to produce or break down other natural chemicals. Purine metabolic disorders arise when crucial enzymes in the biosynthesis or recycling of purine nucleotides are defective or absent.

metabolites

Small molecules that are generated by conversion of other molecules in the body: for example, sugars are among the metabolites arising from digestion of food; xanthine is a metabolite on the pathway of the breakdown of purines to uric acid for excretion. Laboratory analysis of the amount and identity of metabolites in blood (plasma or red cells) or urine can be used to identify defects in the enzymes that carry out the conversion steps. The whole spectrum of metabolites in a given sample may be referred to as the ‘metabolome’.

mitochondria

Small organelles, surrounded by a double membrane, found within mammalian cells; mitochondria (singular: mitochondrion) are often referred to as ‘powerhouses of the cell’ because enzymes in the membrane carry out reactions to produce ATP, the source of energy for chemical reactions in the cell. Each mitochondrion contains several copies of circular DNA which encodes 37 genes, a tiny number compared with about 22000 genes in the chromosomes in the cell nucleus, but these genes are crucial to the structure of the organelle. The mitochondrion also contains many protein components provided under the control of the DNA in the nucleus. Apart from energy supply, several other important reactions are carried out within mitochondria: these include control of calcium levels, an essential step in the biosynthesis of pyrimidine nucleotides, and the production of urea in the liver.

MNGIE

MNGIE (Mitochondrial neurogastrointestinal encephalopathy) is a rare inherited disorder that particularly affects the digestive and nervous systems, with symptoms, such as weight loss, gradually worsening from childhood. It is caused by a deficiency in the enzyme thymidine phosphorylase, which leads to an accumulation of the metabolite thymidine in the body. Excess thymidine is especially harmful to the mitochondrial DNA (see above), and the ability of the mitochondria to provide energy from food is decreased, making the muscles and nerves of the digestive tract less effective at moving food through the system. Inheritance of the faulty gene follows the autosomal recessive pattern.

monosodium urate/MSU

The sodium salt of uric acid, which accumulates in tophi (singular tophus) or as crystalline deposits in the joints.

nephrologist

A specialist in the study and management of kidney disorders.

nephropathy

Disorder of the kidneys, which may reduce the ability to filter chemicals and to produce urine.

neuropathy

Damage to or disease affecting nerves, which may impair sensation, movement, gland or organ function, or other aspects of health, depending on the type of nerve affected.

NSAID

Non-steroidal anti-inflammatory drug – generally used and referred to as pain killers. These include ibuprofen, voltarol (diclofenac) and etoricoxib. They should be used for as short a time as feasible.

nucleic acids (DNA and RNA)

Very large molecules whose structure contains and transmits genetic information.

nucleotides/nucleosides

Nucleotides have one or more phosphate groups attached to the nucleoside, in which a purine or pyrimidine base is attached to the ribose sugar molecule. Nucleotides may be linked into long strands of RNA or DNA, or may fulfil many other roles in the production of energy and other metabolites in the cell.

obesity

Accumulation of fat in the body, giving a final body weight at least 20 per cent higher than recommended for the person’s height and build.

ODC and OPRT

Abbreviations for the two enzymes whose activities are found in the single molecule of UMPS. Defects in one or other of these activities may lead to anaemia and other symptoms.

osteoarthritis

Degenerative damage caused by wear on the cartilage in joints, especially load-bearing or damaged joints. The pain and stiffness progress slowly and chronically, and movement may be restricted.

pH

A measure of the acidity (low pH values, below 7) or the alkalinity (high pH values, above 7) of a solution. Pure water has a neutral pH of 7.0, while blood is normally slightly alkaline, about 7.3 – 7.4.

plasma (blood plasma)

The yellowish liquid part of blood. The plasma is separated from the blood cells when chemicals that prevent the blood from clotting are added at the time of collection. When measuring the concentration of sodium urate in the blood, the resulting figure is the ‘plasma urate level’. See also serum.

PNP

Purine nucleotide phosphorylase – an enzyme involved in transforming and re-using purine nucleotides within our cells. Defects in this enzyme may cause developmental delay, and severe immunodeficiency (SCID) by preventing development of the T-lymphocytes which protect against viruses. The gene for this enzyme is found on the X chromosome.

podagra

Gouty arthritis in the big toe.

prenatal diagnosis

Testing to check for the possible presence of a genetic problem in the unborn baby. The methods used are chorionic villus sampling (CVS) in the first three months, or amniocentesis or sampling from the umbilical cord in the third to sixth months. These tests take tiny samples of cells or blood from the developing fetus. Some centres may use a new method investigating DNA in the mother’s circulation.

primary gout

Gout caused by high levels of uric acid in the blood of middle-aged men, which arise either from the diet or from a natural over-production of purines.

proband

The first member of a family to be identified with an inherited medical condition: if other relatives have similar symptoms, they may also be investigated to study the disorder and to identify how the faulty gene is passed down the family tree.

protein

Essential components of all living organisms, as enzymes, as hormones or as structural components. Proteins are composed of strings of amino acids, most of which are in turn obtained from recycling proteins in the diet.

PRPS

Phosphoribosyl pyrophosphate synthetase – a crucial enzyme in the early steps to make purines. The gene for this enzyme occurs on the X chromosome. Patients with a ‘superactive’ enzyme will produce excessive amounts of purines and hence of uric acid, thus gout will be seen in affected women and in their male children at an early age, along with deafness and developmental delay.

purine(s)  

Natural chemicals containing nitrogen, carbon, hydrogen and oxygen forming a ‘base’ (adenine or guanine). When attached to ribose, a sugar, the nucleosides adenosine and guanine are formed, and with the addition of phosphate, a purine nucleotide is formed. Purine molecules are released by breakdown of nucleic acids and energy metabolism and are converted into uric acid by the enzymes in the liver. Deposits of uric acid salts underlie the formation of tophi and cause gouty arthritis.

purine nucleotides

Single molecules of adenosine or guanosine phosphates (see ATP); they take part in the metabolic reactions in the cells, and are also components of the nucleic acids.

pyrimidine(s)

These natural chemicals are bases (uracil and cytosine) which are modified to form nucleotides, in parallel with purines (see above). Thymine is a pyrimidine base found only in DNA; uracil is used only in RNA. All are released from nucleic acids in the diet, but the breakdown products are dissolved in urine and do not form crystals.

recessive

A genetic term indicating that a metabolic disorder is caused by a deficiency or defect in an important enzyme in the cell.

renal calculi

See kidney stones.

renal failure

Failure of the kidneys to filter or excrete urine; it may be acute or chronic.

rheumatologist

A specialist in the study and management of disorders of joints, bones, muscles and ligaments.

RNA

See nucleic acids.

SCID

Severe combined immunodeficiency, a life-threatening defect in the immune system which defends us from infection. Patients may lack either the antibodies or the lymphocytes that attack foreign molecules, viruses or microorganisms in the blood. See ADA and PNP.

secondary gout

Gout caused by another disease (for example, one of the purine metabolic diseases) or induced by a drug.

serum

The clear yellowish part of the blood, obtained after clotting. Laboratory tests for molecules such as sodium urate may use serum or plasma.

sodium urate

The sodium salt of uric acid, which accumulates in tophi (singular tophus) or as crystalline deposits in the joints. Crystals of sodium urate have a distinctive appearance under polarised light; this can be used to differentiate them from other crystal deposits, such as calcium pyrophosphate dihydrate, which may be found in joints or in the kidneys. (see also MSU)

solubility

The extent to which a salt or other chemical compound can be dissolved in water or body fluids. As more of a chemical is added to the fluid, it becomes a ‘saturated solution’, in which no more can dissolve; it may then begin to form crystals or other deposits, especially as the solution cools. Solubility may be affected by the acidity of the solution; for example, uric acid is less soluble when the urine is more acid than usual.

steroid

See corticosteroid

synovial fluid

Fluid in the space between the two parts of a moving joint (i.e. within the cavity of a joint), for example, knee, toe, elbow.

theophylline

A purine-like compound from the leaves of the tea plant, it relaxes smooth muscles such as those in the breathing passages or blood vessels. It can be used as a bronchodilator to control bronchial asthma.

thymidine phosphorylase

This enzyme carries out a crucial step to ‘salvage’ or recover pyrimidine nucleosides formed during RNA or DNA degradation. A deficiency of the enzyme causes MNGIE disease because the accumulation of the metabolite thymidine interferes with the normal functions of mitochondria.

tophaceous gout

The presence of tophi (see next definition) may be the only evidence of gout in some people, such as older women taking diuretic therapy or boys with Lesch—Nyhan disease. (See also chronic tophaceous gout.)

tophus

(plural = tophi) A solid deposit of sodium urate and membranous structures, typically under the skin or in the ear cartilage. They may reflect sites of earlier damage to joints of the fingers or other parts of the skeleton. Rarely, a deposit may be found in the vertebrae.

TPMT

Thiopurine methyl transferase – an enzyme that modifies some drugs such as azathioprine; patients may have small modifications to the enzyme which will affect the drug’s efficacy or toxicity. Analysis of the activity of this enzyme is strongly recommended before patients receive thiopurines, which are prescribed for chemotherapy and immunosuppression.

ULT

(urate-lowering therapy) The use of drugs such as allopurinol or uricosuric agents to remove urate salts from circulation in the blood.

UMPS

Uridine monophosphate synthase; an enzyme carrying out two of the steps that make pyrimidine nucleotides. If these activities are missing, the patient may have anaemia, immunodeficiency and neurological deficits. Oral uridine therapy may be useful if the case has been diagnosed early enough.

ureter

The tube connecting kidney to bladder, and hence transporting urine to the bladder.

urolithiasis

Stones (derived mainly from insoluble deposits of uric acid) in the urinary tract.

uric acid

The end-product of the reactions that break down purines in humans. Uric acid is excreted through the kidneys and also through the gut, in bile. The salts of uric acid (urate compounds) are insoluble, hence their tendency to form crystals.

uricase

(or urate oxidase) This enzyme is found naturally in all mammals except for man, the higher apes, and some breeds of dog. It converts uric acid to a more soluble compound, allantoin, with the release of a molecule of hydrogen peroxide. Human physiology has adapted well to the lack of the enzyme; uricase may only be really necessary when there is an urgent need to reduce the concentration of urate in the blood of cancer patients. A short course of artificial or modified uricase (e.g. rasburicase, or pegloticase) may be used during chemotherapy to relieve the massive release of urate from lymphomas or leukaemia. The enzyme preparation is administered by injection.

uricosuric drugs

Drugs that help to promote the excretion of uric acid in the urine by preventing the re-absorption of uric acid in the kidneys into the blood.

uridine

One of the pyrimidine nucleosides: the base uracil attached to a ribose sugar.

vegetarian diet

A diet that excludes animal meat and often also fish. Most vegetarian diets allow dairy products because animals have not been killed in the process of production, but vegans do not eat any food connected with animals. A vegan diet is often deficient in vitamin B12.

vitamin

An essential component of the diet, necessary to help in crucial metabolic steps, but not made in our bodies. A balanced diet should provide the required amounts of vitamins and essential minerals, with the exception of vitamin D, which is often deficient during the winter months. Those relevant to gout include vitamin C, obtained from fruit and vegetables, which in high doses has a uricosuric effect; on the other hand vitamins B2 (riboflavin), B3 (niacin, nicotinic acid) and nicotinamide, obtained from cereals, tend to prevent the excretion of urate in urine.

X chromosome

One of the ‘sex’ chromosomes. Women have a pair of X chromosomes, while men have one X and one Y. The genes for some sex-specific stages in development are found on the Y chromosome, so they determine whether the child will be a boy or a girl. The cells in females use (or ‘express’) only one X chromosome: a random choice is made early in development and so each cell expresses either of the two X chromosomes.

X-linked disorder

When one of the genes on the X chromosome is faulty, a boy who carries it will be affected, because he has only the faulty copy and thus a defective enzyme is made. In a recessive disorder, a girl will usually be helped by the presence of an intact copy of the gene on her other X chromosome, allowing ‘good’ enzyme to be made in half of her cells. Very rare cases have been reported, showing that some girls can in fact suffer from an X-linked recessive disorder, usually in a milder form than would be seen in a boy, if the ‘good’ X chromosome is used in fewer than half of the cells of the body.

xanthine

An intermediate in the breakdown of adenosine and guanine to uric acid. Xanthine concentrations will rise when allopurinol blocks the enzyme reaction that should produce uric acid. In high concentrations, xanthine may also form kidney stones.

xanthine oxidase

The enzyme that breaks down hypoxanthine and then xanthine to form uric acid in man. This enzyme is inhibited by allopurinol to varying degrees depending on the dose.

XDH

Xanthine dehydrogenase – an alternative name for xanthine oxidase. Patients with XDH deficiency may have kidney stones containing xanthine and will excrete little uric acid.