An immunologist has urged Malta to allow couples the option of free genetic testing to help prevent rare diseases that he believes are the result of generations of inbreeding.

“Genetically, we are like fourth cousins,” says Keith Sacco, a visiting specialist at Saint James Hospital every six weeks, where he sees many patients with rare diseases.

He believes Malta has more rare diseases than have been described genetically.

Sacco has experience with undiagnosed diseases and can say when a condition does not really fit into a standard described diagnosis.

He gives as an example a rare disease called Griscelli Syndrome. Maltese patients look different from what is reported in the literature describing the condition, Sacco explains.

Griscelli syndrome is a “one-in-a-million” type of disease. But in Malta, there are eight cases.

Malta also has one thymus transplant patient – again another ultra-rare condition. The whole of the US has 20.

Malta has one thymus transplant patient – again another ultra-rare condition. The whole of the US has 20- Keith Sacco

Other doctors too have recognised that certain diseases, related to the metabolism and skin, are not the run-of-mill cases reported elsewhere in Europe, he says.

He says he “would put my medical licence on the line” that there are new diseases in Malta that have never been genetically described.

The consultant immunologist, who is also an allergy specialist at the Royal London Hospital, has put this down to inbreeding since the 1500s.

Sacco’s claim may not be the result of formal studies, but it is based on first-hand experience, his own testing on patients, mechanistic medicine – and intuition.

“I am getting a clear picture from seeing patients all over the world” – and particularly from the NHI, America’s research hospital, where the biggest medical discoveries, including chemotherapy, were made.

An associate professor at the Mayo Clinic College of Medicine & Science in the US, where he trained and eventually grew the children’s immunology transplant programme for its Arizona branch, Sacco is concerned about undescribed rare diseases back home.

‘We are very related in Malta’

A proponent of genetic testing, Sacco insists that “we do not realise we are very related in Malta”.

“The problem is that we breed with each other, as happens in countries like Iceland, which has its own diseases and where free genetic testing is offered to counter the many birth defects in the first year of life.”

In Iceland, another country with a small population, couples are able to use a website called Íslendingabók to check whether they are closely related to each other before the relationship gets serious.

While blanket genetic testing could be risky, Sacco believes that if a couple wanted to do a test before having a child, particularly in view of rare and fatal diseases, it should be freely available.

While more affordable now, the bottleneck lies in getting genetic counselling about the result, although this is getting easier online, he said.

Despite top scientists and immunologists at the University of Malta, Sacco said a specialised clinical immunologist is also absent in Malta.

The unreported genetic changes in the Maltese he has seen could shed light on cancer inflammation in the bowel and inflammatory neurological conditions, such as Guillain-Barré syndrome.

Some genetic variants could also explain so many early onset strokes, particularly in Gozo, Sacco believes.

Genes of interest

In Malta, where he practises immunogenetics, Sacco has started genetic testing and has seen “genes of interest” that would take time to study.

“With rare diseases, for example, you do not have the benefit of, say, 5,000 people you can treat. And you cannot get randomised trials in every domain because of the low number of patients and the poor description.

“But when you start to dissect diseases that are hard to measure, you see a mechanism and you build up patterns from experience and mechanistic data,” Sacco explains.

“With rare diseases, it is not about 50 years of data, but more like five,” Sacco explained.

“Five years ago, we knew of around 50 genes that could manifest in disease if problematic. We now know over 500 such genes. In my short time doing this, my group alone has described seven of these.”

But interpreting the raw data of Maltese DNA is not easy because of the many genes that are not yet understood; as well as changes in genes that have not been reported.

Trials and access to drugs

Opening up to genetic testing would also help patients access expensive drugs, Sacco suggests.

“It is hard for the government to negotiate the rates of drugs that could cost €300,000 a year. But if you create trials for these companies, they could be made available.

“We should start facilitating companies to do trials for potentially life-saving gene therapy on patients in Malta. The patients are here, and it would be of mutual benefit.”

For rare diseases, he called for a better network with other hospitals because “finding the gene is not a one-person show and needs collaboration and research”.

Sacco called for the strengthening of Malta’s collaboration not just with the UK but also in Europe.

“I like the idea of the Dwarna project (the first-ever bio-banking research that focuses on the Maltese genome), and we should also be resequencing patients with certain diseases more broadly.

“The question is how to utilise that data, but there is a great opportunity here. We need to look at it with the right mindset, otherwise we will miss stuff,” he cautioned.

“We need to ease matters for people suffering from rare conditions. Once we know the genetics, it would facilitate the process.”