Common bone conditions such as osteoporosis are well identified and treated, though rare bone diseases still continue to remain rare. There has been a sudden increase in rare diseases in the Middle East as well.
In this interview, Philip Beales, Professor of Medical Genetics, explains the genetic causes of rare diseases and how the UCL Institute of Child Health (ICH) has shed light on a key enzyme involved in the development and maintenance of bone which could help find future therapies to treat rare and common diseases. LMS (Lenz-Majewski Syndrome) which has been identified by the international study as the mutated gene in people is a skeletal disorder which causes bone malformations and also affects the brain. So far, only ten cases of this syndrome have been identified.
Question: What is a rare bone disease?
Answer: It’s literally numbers– in the sense that the condition is present in the population in less than one or fewer than one in 2000 persons. In such cases, it is considered rare. Of course, it is not a very helpful term, but it is helpful when you consider that there are around 6000 described rare entities or rare diseases in their own right.
So you will find that some of these are clearly incredibly rare, one in a million. So bringing them all together, actually it is a convenient way of addressing what is becoming an unmet need in a large population. The fact that having this disease isn’t very common, most health services aren’t geared up to dealing with people who have this unusual condition, they are more geared up to dealing with blood pressure, diabetes and obesity.
One of the problems you will always hear from patients is this diagnostic odyssey is that patients go many years without a diagnosis and that has been the case for a long time. But the changes in the genetic technology has now enabled us to rapidly get to a diagnosis that previously had been left. And the care for patients with rare diseases is usually suboptimal for the same reasons that the health services are not geared up to looking after them. But to take care of these patients is a multi-team approach.
Q: What are the genetic causes of rare bone disease?
A: As I said, on the web and on various databases, there are now about six to seven thousand listed rare genetic disorders described in detail. Only 2,300 of those actually have a gene associated with them and the underlying fault in the particular gene. There’s still at least two-thirds of these to be sorted out, but there are a number of international and national programs that are going on where the majority of these conditions will be solved.
I think in about four to five years time from now, we will be able to solve about up to a 5000 out of the 6000. But the benefit of finding the genetic cause of a particular condition, particularly a rare one or even a common one is that it’s multi-folded because the first thing is you instantly have a diagnostic test, so not only does it confirm the disease in that patient, it also enables a carrier test to be developed for other members of the family who might be at risk, brothers or sisters.
And then the final component obviously of understanding the genetic cause of any condition is that it can tell you how that disease arises and what are the developmental processes that cause the disease, which is a prerequisite for thinking about therapies and so now we are getting nearer to many of these conditions and we are able to think about instant therapies or develop therapies like gene therapy.
Q: Is the number of rare disease in Kuwait very high?
A: Yes, it is very high because of the simple fact that the cultural norm is to marry within the family and so it’s not a character problem in any way. It’s simply that you are increasing the statistical probability that you are going to keep, if its what’s called a recessive disease. The number is also high in Bangladesh, Pakistan and India.
Q: How do rare diseases develop? Does it start very early in children or does it come with age-related changes?
A: It depends on the disease; you can have a disease that’s affecting just one part of the body, like the eye in the form of blindness. Some of the conditions I work on have blindness but affects virtually every part of the body, so they would have obesity, diabetes– that’s actually one of the most common conditions in the rare disease.
A condition called Bardet-Biedl syndrome has been documented on being a more common rare disease in this country, and the most common rare disease in Europe is Cystic fibrosis. But for the Bardet–Biedl syndrome, there may be one in 50 people or more in this country are carrying it, so it’s one of the most common ones in Kuwait and it affects every part of the body. The problems could be obesity, diabetes, blindness, kidney failure, some kids are born with extra fingers and toes. About five to 10 percent of the children affected by this disease will not make it to their fifth birthdays.