Few doctors have genetic disease on radar

Derbhile Dromey on a disease which is the second-most common fatal genetic disease in Ireland but has a low profile with many doctors

Alpha-1 anti-trypsin deficiency is the second most common fatal genetic disease in Ireland. Yet few people, even medical professionals, have heard of it. The condition affects the lungs and liver. Because the symptoms are similar to those associated with other respiratory and liver diseases, there is a high level of misdiagnosis.
The Alpha One Foundation runs a national screening programme intended to help the medical profession make a clearer diagnosis. The group recently wrote to the Irish Times, highlighting the impact of the long waiting list for transplants at the Mater Hospital on alpha-1 patients.
The disease is caused by a mutation in the genes for alpha-1, the anti-protease which protects the lungs against the effects of bacterial disease and cigarette smoke. In 10 per cent of cases, it causes liver disease.
Alpha-1 patients will present in a GP’s surgery in a similar way to patients with COPD, asthma or emphysema, but without the usual triggers, such as long-term smoking or occupational exposure to toxins. It’s a slow-onset disease, with symptoms such as wheezing and shortness of breath building over time.
The process of diagnosing alpha-1 is fairly straightforward. Patients can give themselves a finger-prick test with a self-injection kit, or present to their GP. They can send the sample in a stamp-addressed envelope to the National Screening programme to be tested.
The level of alpha-1 is measured in the blood, along with albumin and antibodies. If levels are low, the blood is subjected to a further genotype test under the national screening programme, which proves conclusively that the patient has the defective alpha-1 gene. These patients have approximately 5 per cent of the normal level of alpha-1.
Misdiagnosis
Tomas Carroll is an associate lecturer at RCSI who is also responsible for running the Alpha One Foundation’s screening programme. He attributes the high level of misdiagnosis to lack of awareness and to the comparative newness of the condition.
“It was first described by two Swedish doctors in 1963,” he says, “so if you take that into account, there’s 20 years before a condition becomes bedded down in teaching literature. There were diagnoses, but they were often incidental diagnoses.”
Incidences of alpha-1 anti-trypsin deficiency are almost as common as those of CF.
The genes of patients with Alpha One commonly contain two mutations, labelled s and z. Researchers at St James’s Hospital have tested a randomised sample of donated DNA and found that 10 per cent of the samples contained the s mutation and 5 per cent carried the more severe z mutation.
These figures were higher than expected. From the data, it’s possible to deduce that 2,100 individuals are likely to developing alpha-1. That works out at one in 2,000 Irish people.
Yet the condition is at the root of only 1 per cent of pulmonary cases. So how big is an issue is it for GPs on the front line? Dr Charles Daly, who has a practise in Dungarvan, Co. Waterford, has never encountered an alpha-1 patient in his practice.
“I’d be hard pressed to say I’ve ever seen a case of it. As a student in Crumlin, I would have seen it. It’s not something you’d see every day. I wouldn’t be looking for it unless there were unusual features.”
The Alpha One Foundation’s screening programme was set up by Professor Noel McElvaney of Beaumont Hospital and is funded by the Government. Patients diagnosed under the screening programme are referred to him for treatment. Prof McElvaney also secured funding for a research lab, where patients can take part in clinical trials.
Liver disease
The screening programme began in May 2004 and targets patients with COPD, non-responsive asthma and cryptogenic liver disease, in accordance with WHO guidelines.
It also targets relatives of patients diagnosed with alpha-1, which has meant that patients who were asymptomatic can begin treatment sooner. To date, it has screened 3,500 people.
Over the past year, the Foundation has redeveloped its website, which is attracting a lot of visitors. Patients themselves have become involved in advocacy and promotion through the patient support group.
The ICGP has released an impact statement on the effects of pulmonary disease, which mentions alpha-1.
At present, the Alpha One Foundation is targeting respiratory and liver clinics rather than GPs. However, it has hosted two GP meetings, one in Cork and one in Galway, where a lot of new cases have been diagnosed. It is discussing the possibility of a targeted regional mailing campaign and aims to present at the ICGP conference next year.
Tomas Carroll says the effects of the awareness campaigns in the clinics will filter down to GPs. “We’re diagnosing people through clinics and people’s siblings and children are presenting to GPs down the country. In the last year and a half, we’ve seen an increase in the number of finger-prick kits being sent to us from GP clinics.
It’s like a slow drip that’s building into a steady stream. There’s nothing like a positive diagnosis in a GP clinic to raise awareness.”
Once a patient has been diagnosed, GPs should advise on lifestyle modifications that patients can make and ensure that infections are treated early and aggressively.
Dr Mark Walsh, a GP in New Ross, Co Wexford, says that even if they encounter it rarely, GPs should still bear it in mind; “Keep an enquiring mind, particularly if a patient presents with symptoms that don’t match the typical profile. It’s small-print stuff, but GPs should keep it on their radar.”