Rare diseases are difficult enough to diagnose, but some have symptoms that change with age, making diagnosis even more difficult.

Fabry disease is an inherited rare disease in which a mutation in the GLA gene of the X chromosome causes the body to lack the alpha-galactosidase A enzyme. This causes undecomposed substances to accumulate in the cells, leading to abnormalities in organs such as the heart and kidneys.

“Depending on what age (Fabry disease) patients are, the main symptoms are completely different, so it is difficult to diagnose them,” said Professor Sohn Young-bae of the Department of Medical Genetics at Ajou University Hospital, on the Korean Organization for Rare Diseases’ YouTube channel “Angels Spoon TV.”

So, what is the course of Fabry disease?

“Patients start to experience symptoms in childhood, and there is a slight difference between male and female Fabry disease, with male patients experiencing symptoms earlier and progressing more severely, and female patients experiencing symptoms later and progressing more slowly,” Professor Sohn said.

Still, both sexes usually experience symptoms in childhood. Boys first experience symptoms around age six or seven, and girls often experience symptoms in the upper elementary and middle school years, Professor Sohn noted. The first symptoms of Fabry disease are hand and foot pain, corneal clouding, and abnormal sweating.

“The most common symptoms in childhood are peripheral pain. Some people describe it as a burning or stabbing sensation,” Sohn said. “It's characterized by paroxysmal pain. The problem is that these symptoms are usually normal on routine medical tests.”

It is difficult to suspect Fabry disease in the early stages because all the tests come back to normal. Over time, other symptoms gradually develop, and organ damage occurs. Later, there are kidney problems, proteinuria, and a gradual decline in heart function.

For this reason, it often takes a long time for people with Fabry disease to be diagnosed. Because it's so rare, it's not always easy for doctors to suspect Fabry disease in the first place; symptoms vary with age, and there's no specific test to screen for Fabry's disease in routine hospital tests.

“It is often not until the 20s in men and 30s in women that patients with Fabry disease are diagnosed,” Professor Sohn explained. “The early symptoms are very non-specific, easily mistaken for many other diseases, and there is no specific point in a typical blood test that differentiates Fabry disease from other diseases, so it can take a long time to differentiate from other diseases.”

However, Fabry disease is a rare condition that requires early diagnosis. Because Fabry disease is a progressive disease, it gradually destroys the body's organs, and once it reaches a certain point, it is impossible to return to normal, so early diagnosis and treatment are crucial to prevent the disease from progressing.

“Fabry disease is a progressive disease, and if you treat it after it has already progressed a lot, it reaches a point of no return, which is called the point of no return, and even if you treat it, you can't make it normal again, so it is very important to diagnose it early and treat it early before the patient gets too bad,” Sohn said.

Very specific symptoms can also lead to suspicion of Fabry disease in children when symptoms first begin.

“The symptom of having pain in the hands and feet but not sweating is more characteristic than you might think,” Professor Sohn noted. “Young patients don't sweat because their peripheral nerves and autonomic nervous system are not well regulated. It's very hot, and they're not sweating at all, they're dry. If you're in a very hot situation and don't sweat at all, you're dry as a bone.”

In addition to these symptoms, newborn screening has provided another way to identify Fabry disease patients early since January of this year. The newborn screening test can be used to detect asymptomatic Fabry disease patients, and then family testing can be used to identify additional Fabry disease patients so that they can be treated quickly.

“Fabry disease is a disease where family testing is very important,” Sohn said. “According to reports from other countries, once a Fabry disease patient is diagnosed in a family, there are about five additional patients in the family, and there are likely other hidden patients in the family who have not been diagnosed because of the mild symptoms.”

Notably, if a newborn is diagnosed with Fabry disease at newborn screening, that newborn is asymptomatic. However, on the maternal side of the family, some patients may already be adults. So, family testing may be more critical in patients diagnosed at newborn screening, he noted, explaining that Fabry disease is often diagnosed in both sons and mothers.

If Fabry disease is confirmed through family testing, early treatment is important. However, some patients are reluctant to seek diagnosis and treatment.

There are many patients, especially women, who feel that their symptoms are not so severe, or that when they were younger, they had pain and were uncomfortable, but as they get older, the pain disappears and the heart thickens, but they don't feel uncomfortable. So, there are patients who are very reluctant to get diagnosed or start treatment, according to the Ajou University Hospital professor.

“It is often difficult to reverse Fabry disease once it has been delayed and the patient's condition has deteriorated, so it is very important to test early and start treatment early, even if the symptoms are not severe, to help the patient maintain a normal life later on,” Professor Sohn said.