Fabry Disease: New Oral Treatment Improves Quality Of Life 

What is Fabry Disease?

Fabry disease is a serious rare genetic disease characterized by the accumulation of sphingolipids (a particular sugar group) in lysosomes, a type of organelle that breaks down many types of molecules.

It is caused by the mutation of the alpha-galactosidase A (a-Gal A) gene, which results in the absence or dysfunction of the enzyme. The defective gene can be found on the X chromosome, which means it is transmitted through X-linked inheritance. For this reason, the most serious form of the disease is found in males since they have only one X chromosome. Females, instead, normally only have mild symptoms given they have two X chromosomes and one of the two is normal. In any case, the symptoms and development of the disease may vary greatly, even within the same family.

Typical symptoms, normally first experienced in childhood, include:

  • fever
  • fatigue
  • pain to the extremities
  • tiny papules that appear on the skin
  • lack of sweating
  • clouding of the corneas

Throughout one’s lifetime, the disease compromises and strikes different organs, including the nervous system, kidneys, the heart and the arteries. More severe cases can result in kidney failure, heart attacks and strokes.

The annual incidence of Fabry disease in Italy is around 1 in 80,000 people, yet the prevalence is slightly underestimated because it does not consider the variants of patients with late-onset.

How is Fabry disease transmitted?

Fabry disease is transmitted differently in men and women given that it is linked to the X chromosome.

The X chromosome transmitted by a man results in a female child, while the Y chromosome transmitted by a man results in a male child. Thus, a father affected by Fabry disease:

  • will transmit an X chromosome with a defective alfa-gal gene to all of his female children;
  • will not transmit an X chromosome with the defective gene to any of his male children.

A woman transmits an X chromosome to both male and female children. If she is affected by Fabry disease, normally only one of her X chromosomes will have the defective alfa-gal gene, meaning that:

  • there is a 50% chance that she will transmit the defective chromosome to her male or female children.

Late diagnosis is a problem

The earlier Fabry disease is diagnosed the better given that over time the disease progresses, bringing about irreversible damage to organs. Unfortunately, the disease may be difficult to diagnose for several reasons:

  • Since it is a rare genetic disease, many doctors do not initially consider it as a possibility;
  • Many symptoms can easily be attributed to more common pathologies;
  • The disease normally affects different organs that are often treated by different health specialists, making it more difficult to recognize symptoms as being linked to a single cause;
  • Several exams must be done before confirming diagnosis of the disease.

An enzyme assay is the first step in diagnosing Fabry disease, especially in males, which is generally confirmed genetically at a later date. In heterozygous females, instead, the enzyme assay is not conclusive and must be confirmed through a genetic test.

It is thus fundamental to promote awareness of Fabry disease for early diagnosis. With this in view, we would like to point out #ViverelaFabry, a communication project carried out by the Observatory of Rare Diseases.  

Available treatment

Two types of therapy are currently available:

  • enzyme replacement therapy, which is carried out every 15 days via an intravenous infusion;
  • oral pharmacological chaperone therapy, which is effective in patients with “amendable” mutations.

Andrea Benso, specialist in endocrinology and metabolic disorders at the SCDU Department of Endocrinology, Diabetology and Metabolic Disease, explains the difference between the two, “Each form of treatment has a different function. Intravenous enzyme therapy allows us to directly introduce the missing enzyme, giving the patient 15 days of protection. This is why infusions must be repeated every two weeks, theoretically, for an entire lifetime. Oral chaperone therapy, instead, uses a very innovative mechanism of action that is able to restore enzymatic activity where it has been lost, when amendable mutations are present. This treatment is also lifelong therapy”.

Genetic treatment for this disease may be developed in the future.

Unquestionable advantages to oral therapy

Biweekly intravenous infusions either in a hospital or at home through Patient Support Programs, obviously has a great impact on a patient’s quality of life with inevitable psychological consequences. The idea of “lifelong” therapy is also difficult to accept. This is why psychological and emotional support programs (even remote ones) for patients are becoming more and more frequent.

Compared to infusions, the new oral therapy undoubtedly improves a patient’s quality of life in that treatment involves only taking a pill every other day without food and does not influence work, travel, school or life in general. There are some side effects however:

  • over time patients may begin underestimating the seriousness of the disease.  It is important to highlight that treatment does not lessen the seriousness of the disease and therapy must be followed correctly. Medication must be taken regularly without food.
  • patients can feel neglected. Having been used to a continuous and attentive relationship with health care workers, patients may feel a sense of abandonment and isolation with repercussions on the patient’s adherence to therapy. This is a common problem experienced with all new oral therapies.

In conclusion, the new oral therapy is without a doubt a great advancement in improving a patient’s quality of life, but it must be followed carefully and the patient needs support as he or she changes to the new form of treatment.

© Domedica s.r.l.

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