Funded by and developed in collaboration with Chiesi Global Rare Diseases

Professor Camillia Tøndel gives her personal views on the challenges in Fabry disease around screening and diagnosis, and how these strategies need to evolve

By Geoff Case, RARE Revolution Magazine

Interview with Professor Camilla Tøndel, professor of paediatrics at University of Bergen and physician at Haukeland University Hospital, Bergen, Norway

As a hereditary disease, Fabry disease is already present at birth, but it may take many years before symptoms appear. Professor Camilla Tøndel explains that a male patient with a classical mutation may show symptoms at around six to ten years of age, but this depends on the patient: “Some start earlier, some later.”

Initial symptoms of the disease are often unclear, she says, which contributes to delays in diagnosis: children may have to take frequent breaks during sport because of pain; they may go red in the face with a decreased ability to sweat; they may have abdominal problems. Unfortunately, in Camilla’s experience, the nature of these symptoms sometimes means that children wrongly are wrongly labelled as hypochondriacs.

She adds that, often, a person with Fabry disease may not be diagnosed until they are in their twenties or thirties, when they show signs of organ disease, such as kidney or heart problems. Typically, they may have had red bumps on the skin (known as angiokeratoma), burning pain in the hands and feet and abdominal problems, which can be symptoms of the disease, “but nobody put them together” until the diagnosis is made. It is “not seldom”, she says, that a diagnosis is made through a kidney biopsy.

“Awareness of Fabry disease has increased since Fabry-specific treatments became available, but a lot of families still go under the radar.”

While genetic screening has helped to bring many people a diagnosis of Fabry disease, the high number of genetic variants is a complicating factor, Camilla says. Many genetic mutations cause classical disease, and “nonclassical mutations” may also cause severe disease, even if the problems arise later. Other gene variations may lead only to mild disease or not cause disease at all.

Camilla explains how this may potentially lead to problems for somebody who has been diagnosed with Fabry disease but whose symptoms are caused by another condition. “It’s important to find out whether the Fabry diagnosis explains the problems the patient has, or whether it is only part of the picture, so that we can help properly,” Camilla says.

Even when family members share the same gene mutation, the course of the disease can vary. “Because Fabry disease is an X-linked disease, some females may have kidney failure and severe cardiac disease and other females may appear to be totally healthy.”

X-linked disease: Males have one X chromosome and females have two. If the healthy X chromosome dominates in a female, she will have milder symptoms of Fabry disease or no symptoms at all.

The genetic complexity of Fabry disease makes it unsuitable, Camilla believes, for inclusion in genetic screening of newborns. She emphasises how, in many countries, predictive screening for a condition is only allowed when detection of it is likely to bring a clear benefit to the child. In Fabry disease, she argues that is not always the case, and decisions to screen asymptomatic children must weigh up the benefits.

“Screening neonates [newborns] could make some children and families feel ‘diseased’ without being diseased. They could get the message they have Fabry disease before we are sure—maybe for a long, long time—that they have a mutation that is disease-causing.”

The consequences of a diagnosis at birth are wide-reaching, Camilla believes. Health insurance may become impossible in some countries, and the person may unnecessarily limit their aspirations, waiting for health problems that may not arise. “Nowadays, we have so many opportunities to know about our genes, but many mutations are not going to make any problems for us.” In her view, family members should be able to choose whether to be tested or not.

For Camilla, good care in Fabry disease means “diagnosing quickly, checking what kind of mutation it is, and then personalising the approach with the patient—focusing on the people who need help”.

She believes that genetic screening that is diagnostic, rather than predictive, is valuable: “There should be a low threshold to screen for Fabry disease if there are unclear clinical findings to do with the kidneys, heart or central nervous system.”

An early diagnosis of Fabry disease can help to potentially improve a person’s quality of life, she says. It gives doctors the opportunity to treat a child’s pain and make it clear that the pain is not dangerous pain; and that it will be good for their general health if they live an active life. She warns that doctors must also be careful as they describe the potential severity of the disease, as it is not the case that everyone will be severely affected.

However, quicker diagnoses depend on health care practitioners’ thinking of Fabry disease when somebody comes to them with the typical symptoms. Greater awareness is, therefore, vital.

“I think part of the problem is that some paediatricians don’t know [about Fabry] or don’t think about Fabry, because it’s seldom seen,” Camilla says. She wants to see people being diagnosed before adulthood, when severe organ damage may already have happened.

Once the person has a diagnosis, Camilla would like to see personalised care pathways. She believes that there needs to be careful thought about when treatment should start, weighing up the risks versus benefits.

In general, she explains, males with classic Fabry disease tend to be treated at an earlier stage, as are some women with a “male phenotype”, who may have as severe a form of the disease as males. But prioritising treatment—supportive treatments as well as Fabry-specific treatments—for the patients that need it most is very important. “We should treat the patients in an individualised way, and not take a too general approach,” she says. It is important, she says, that “health care professionals strive for a balance, individualising care pathways and following up in a thorough and caring way”.

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Content developed by RARE Revolution Magazine in collaboration with Chiesi Global Rare Diseases (GRD). All opinions are those of the contributor. RARE Revolution Magazine retains all copyright.

UK-CHI-2300759 January 2024

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