More to come? J.J. HAUW/SCIENCE PHOTO LIBRARY

It’s finally happened. Until now, vCJD – the deadly disease caused by infection with BSE, or “mad cow disease” – has struck only people with a certain genetic makeup. Now, for the first time, researchers have confirmed a case in someone with different genes – a finding that could mean we have been misdiagnosing a new wave of cases.

In late 2014, a 36-year-old man in the UK started developing aggressive personality changes, memory loss and problems walking. The symptoms and brain scans were typical of ordinary CJD, a rare disease of elderly people not linked to BSE. But because he was so young, his prions were double-checked after he died in February 2016. In fact he had vCJD, the kind caused by BSE.

The surprise was in his DNA. BSE is caused by a misshapen protein, called a prion. It spreads when prions in the blood interact with the normal version of the protein, and pass on the deformation. These prions build up in the brain, eventually causing neural disorders and death.


But the normal protein comes in two forms. Either it has the amino acid methionine (M) at position 129 in the amino acid chain that makes up the protein, or it has valine (V). We inherit a gene for this protein from each of our parents, and there are three possibilities – people whose bodies only make the M form, people who only have the V form, or people who make some of both.

Second wave

All 223 people previously diagnosed with vCJD worldwide, including 177 in the UK, made only the M type of the protein. But the 36-year-old man had a mix of both – the first such case, apart from one unconfirmed case in 2008.

The reason it has taken so long for such a case to appear is likely because people with both types of protein take longer to develop the symptoms of vCJD. Only the M form can be deformed by the BSE prion, and because these people have less M protein, it takes longer for the prion to build up in their body. Kuru, another human prion disease, is already known to take longer to develop in people with both forms of the protein.

Since 2000, cases of vCJD have been declining in the UK. But it is now highly likely that we may get another wave of cases in MV people, says Graham Jackson, at University College London. In the UK, 38 per cent of people make only the M type of protein, while 51 per cent make a mixture of the two.

Moreover, more people in that last group may be infected than we thought. Researchers calculated in 2013 that one in 2000 people in the UK carry the prion, by counting the number of removed appendixes that contained it. But the recent case had no prions in his appendix. If that is true of more people with both M and V proteins, then that survey missed many infected people

Unfortunate few

The second wave might already have started. The rate of cases diagnosed as ordinary human CJD has doubled since the mid-1990s. Part of this is due to better diagnosis, but Jackson says that should have peaked by now – yet cases are still climbing.

As the 36-year-old’s clinical signs looked like ordinary CJD, Jackson fears vCJD in other people who make both variants of the protein might have been misdiagnosed. Many such cases are not given autopsies.

Exposure to BSE prion was at a high level in the UK until 1989, when some of the meat most likely to contain it was taken out of the food chain. So far, no vCJD patients were born after 1989.

Fortunately, it seems these prions only develop into disease in an unlucky few. Even if only 1 in 2000 people carry prion, 6000 cases of vCJD should have developed in people making only the M protein by now.

Journal reference: New England Journal of Medicine , DOI: 10.1056/NEJMc1610003