About purine disorders

Purines: what are they?

Purines are chemicals which are basic to life. They give us our energy and, with similar chemicals called pyrimidines, are in our blood and our genes. Purines and pyrimidines make up a crucial part of both DNA and RNA, and the basis for the universal genetic code.

Metabolism: what is it?

Metabolism is the process by which human cells derive or make vital chemicals from food, or recycle waste from dead cells. For purines and pyrimidines this involves firstly constructing chemicals called nucleotides, and then secondly recycling the purines or pyrimidines released when the nucleotides break down. This happens constantly during exercise, wound healing, the death of red cells, or when white cells respond to invading organisms.

Why purine metabolic patients?

When a defective gene causes gaps to appear in this recycling process, these chemicals are not metabolised properly, and adults or children can suffer from any one of twenty-eight hereditary disorders, possibly some more as yet unknown. Symptoms can include gout, anaemia, autism, epilepsy, delayed development, deafness, compulsive self-biting, kidney failure or stones, or loss of immunity (similar to AIDS).

Some affected babies can spend much of their babyhood in a hospital ‘bubble’ awaiting a bone marrow donor; others can suffer in the first weeks of life from gout and kidney stones, leading, at worst, to dialysis and a kidney transplant. In yet others the first symptoms may be delayed development, anaemia, autism, or epilepsy. All conditions cause untold distress and threaten the unborn. Only some can be treated.

Can they be cured?

No, not so far. A few can be treated, if diagnosed early enough, but many disorders remain crippling or potentially fatal. Where the tendency in the family is known, (often it is not), prenatal testing is possible. Patients can be helped by various means to live with their disability, but there is a family where all three sons have died, others have lost five close relatives, others where babies have had to be nursed in a ‘bubble’ and children who will never walk or talk and may die young. More research is badly needed.

Are these disorders common?

Not at present, but their identification is very recent. Many of the cases now known were originally undiagnosed, or misdiagnosed, for months or even years. There are undoubtedly many more sufferers than are currently recognised; possibly one hundred annually in this country alone.

Why is the research at St Thomas’ Hospital important?

Because these disorders have only relatively recently been characterised, few such laboratories exist and patients and investigators come to St Thomas’ from around the globe. The Purine Research Unit founded in 1970, was the first to recognise some of these disorders. It has devised many new methods of identification and has developed the only diagnostic service for Britain. Its research has already helped many families and saved the NHS hundreds of thousands of pounds.

Because these chemicals are so vital, it is now evident that this research has a much wider application in areas as diverse as heart disease, AIDS, leukemia, cancer or organ transplantation. It may thus assist many more patients.

As a result of its contributions to the field, the laboratory has become the nucleus of a European centre for training in diagnosis and research – a proposal supported by the European Society for the Study of Purine and Pyrimidine Metabolism. This is important for patients and for Britain’s prestige, but substantial funds will be required to continue this work.

If funds are not forthcoming, this research could come to an end and the patients’ hopes will be shattered. This is where PUMPA comes into the picture.

What are the metabolic disorders under the PUMPA umbrella?

[helix of DNA showing complementary base pairing]

Disorders arising from defects (mutations) in genes coding for steps in the complex chemical network which makes our vital nucleotides. Purine nucleotides such as ATP (adenosine triphosphate) supply our body energy and repair our cell membranes. Purines and pyrimidines are also the building blocks of our DNA: purine nucleotides providing the As and Gs, pyrimidines the Ts and Cs, of our body’s genetic ‘library’.

Inability to make a specific nucleotide can damage blood cells and cause severe untreatable anaemia. Without ATP any cell will die. Faults in purine steps which recycle waste from daily cell death/turnover can produce, for example:

  • bizarre neurological deficits, as in Lesch-Nyhan Disease
  • an immunodeficiency disorder ‘baby in the bubble’ syndrome which kills our body’s white cells which resist infection
  • too much uric acid, which causes gout and sometimes severe kidney damage in babies and children as well as adults.

Symptoms to look out for

  • Gout in a young man or woman. Gout in people under thirty is always unusual and should be investigated, not just treated with Allopurinol. Too much Allopurinol can cause kidney damage in young patients with genetic gout.
  • A history of infections which do not respond to treatment along with ‘gravel’ on a child’s nappy or the passage of small stones or loin pain.