OrphaNews Europe first reported on the increased prevalence of rare genetic diseases in the northern England metropolitan area of Bradford in December 2005, following a news article that appeared in the BMJ describing a local Member of Parliament's controversial call for legislation that would ban consanguineous marriages in the UK. Bradford, located in the county of West Yorkshire, has a significant Pakistani community that practices marriage between first cousins, leading to an increased number of rare autosomal recessive disorders in the local population. Indeed, Bradford medical professionals are contending with over 140 different autosomal recessive diseases, whereas other typical districts of similar size in the United Kingdom usually see between 30 and 40 such disorders. OrphaNews Europe presents an interview with a professional who works with this growing group of patients. Bradford-based paediatrician and neurodisability specialist Dr. Peter Corry has worked extensively with rare disease patients in the area and published several studies on the subject:
OrphaNews Europe: How does the increased number of autosomal recessive illnesses impact your community's medical resources?
Dr. Peter Corry: It has an impact on all services from conception and pregnancy, through paediatrics and other child health services towards either transition to adult services or sometimes death during childhood. I am speaking as a paediatrician working in Bradford, West Yorkshire. We cover a population of about 360,000 of whom about 106,000 are under 18 years of age. There are about 6,000 births each year, and about half are now of Pakistani origin. This population has a preference for cousin marriages and also marriage within the clan.
My own speciality is Neurodisability and I work with colleagues in our Child Development Centre. Our patients have learning or physical disability, with conditions such as Down syndrome, autism, cerebral palsy and spina bifida. However we have had an increasing number of patients with rare, usually autosomal recessive genetic, conditions and this also applies to colleagues in other branches of paediatrics here. In the past decade we have identified at least 148 different autosomal recessive conditions in our children. My answers will concern children with all sorts of conditions although, of course, I know most about the ones with neurodisabilities.
Many of the conditions are complex, many will be unfamiliar to staff, many will require liaison between local staff and more specialist teams. With limited resources, priority has to be given to the children with the most need, so that other children may not receive the routine services they would expect elsewhere.
And many of the rare disorders can be complex, affecting several organs. For instance, our patients with Bardet-Biedl syndrome need attention from an ophthalmologist, nephrologist, plastic surgeon and neurologist as well as our team at the Child Development Centre and others. It isn't really possible to cope with all this in a 20 minute clinic session two or three times a year.
Unfortunately, many of these genetic conditions that we see are life-limiting, so we have to consider the increased number of children who may die in childhood. I have looked at deaths in my own patients over a period of 12 years (1993-2004). During that time there were probably nearly twice as many caucasian as Pakistani children in Bradford. 43 Pakistani children died, of whom 23 had an autosomal recessive genetic condition. 30 white children died, and none of them was thought to have an autosomal recessive condition.
An example of the pressure on our clinical team is that we have not yet had agreement to hold joint feeding clinics for children with disabilities. These would be so important to enable colleagues to work together on these complex and often life-threatening problems. We have not yet been able to start either the joint clinics with paediatrician, orthopaedic surgeon and physiotherapist to assess children with cerebral palsy who may benefit from surgery or clinics to assess and treat children with injections of botulinum toxin. And this is in a district with an extremely high prevalence of cerebral palsy. In recent weeks, we have been unable to see new patients within the 11 weeks of referral from family doctors, one of the Government health targets.
OrphaNews Europe: What are some of the more rare disorders that you see?
Dr. Peter Corry: There are now more than 20 children with primary ciliary dyskinesia, about thrice the expected prevalence. These children often have their heart on the wrong side and usually develop a gradually worsening lung condition.
I myself have cared for four children with Aicardi-Goutieres syndrome, from three different families. These children can have severe neurological and developmental problems associated with intracranial calcification. There is a child with aspartylglucosaminuria, which is a condition that usually affects Finnish people. There are three or four children with hyperekplexia (startle disease) and one was reported in the literature when autosomal recessive inheritance was identified. A colleague looks after three children with Cockayne syndrome.
My colleague in haematology has had patients with extremely rare conditions such as protein C deficiency, Bernard Soulier syndrome, factor XIII deficiency and Glanzmann thrombasthenia, as well as the rare but more widely known thalassaemia and sickle cell disease. With factor XIII deficiency it is estimated that there are about 15 children in the area around Bradford out of about 50 in the whole of the United Kingdom.
The local ophthalmologists see many children with unusual types of retinitis pigmentosa and have several patients with familial exudative vitreoretinopathy.
Support from colleagues in specialist centres in the UK, as well as in Europe and America, has been invaluable. The Internet and improving communications generally has been useful, and we are making increasing use of the clinical summaries on Orphanet.
OrphaNews Europe: Can you discuss some of the medical interventions that these disorders necessitate?
Dr. Peter Corry: The range of rare conditions that we see is so broad that I can only mention some of the treatments:
Children with metabolic disorders will often require specialised diets. Some of these will be quite complex. Many will need medication, and some will receive new treatments such as substrate deprivation or enzyme replacement. A few may be considered for bone marrow transplants or other "cutting edge" approaches. Especially for those with disorders of intermediary metabolism, frequent admissions may be needed in order to stabilise their condition.
We have many children with neurological conditions. They may need anticonvulsants for seizures or treatments to reduce spasticity such as oral or intra-thecal baclofen or intra-muscular injections of botulinum toxin. Many need orthopaedic surgery because of complications, such as joint contractures or hip dislocation and a few will have surgery to correct spinal curvature.
Some of the weaker children with neuromuscular conditions may need respiratory support with a ventilator or positive airways pressure when asleep, or even at all times of the day and night.
Artificial feeding through a naso-gastric tube or gastrostomy is needed for many with feeding or swallowing difficulties. Our dieticians treat 182 children who are tube-fed, of whom 50% are disabled children attending the Child Development Centre.
Children with anaemias, coagulation or platelet disorders may need regular transfusions of blood or blood products and may also require drug treatments. Children who have frequent intravenous treatments may need indwelling IV catheters.
The list of options seems to be getting longer all the time as new treatments are developed.
Hospital admissions are required, both for acute illnesses and for planned treatments. Many disabled children will be prone to life-threatening chest infections or may need admission to hospital following severe seizures. Some children may need regular admissions for courses of intensive treatment. This will aim to slow down deterioration, such as for children with cystic fibrosis or primary ciliary dyskinesia.
We do not have an intensive-care facility for children in Bradford so our patients are obliged to go to the regional centre in Leeds (or elsewhere, when it is full). More than a third of the beds in the regional ICU are usually occupied by patients from Bradford, although we have only about 6,000 of the 36,000 births in our region each year.
Many of the children need speech and language therapy, physiotherapy or occupational therapy. Our dieticians are also important for children with nutritional problems. We also have a very good service from children's nurses in the community, or from our hospital outreach team. They may help in the care of children in their homes or schools.
Read the full interview with Dr. Peter Corry
Contact Peter Corry
