Management of Fabry disease

As in Gaucher disease, the management of patients with Fabry disease is based on subclinical as well as clinical parameters of disease severity and progression. However, careful monitoring of subclinical parameters is even more critical in Fabry disease because of two differences. Firstly, in Fabry disease there is a dissociation between initial clinical symptoms like pain (mainly related to the peripheral and autonomous nervous system involvement) and the severe but subclinical disease progression in organs like the kidney and heart, and the latter will actually lead to premature death in many of these patients. Secondly, compared to Gaucher disease, much less of the subclinical disease progression is reversible.

In terms of monitoring a patient, this implies that at regular intervals a multidisciplinary evaluation of all critical organs including kidneys, heart, and brain, is required. Furthermore, the decision to start enzyme replacement therapy (ERT) can be driven not only by symptoms, but also by subclinical evidence of significant disease involvement in any of the key organs. Consequently, all children as well as women should also be monitored carefully for evidence of subclinical disease progression.

In terms of treating a patient, there are two distinct goals of therapy. One is to alleviate the symptoms the patient is experiencing, and the second one to prevent the late, life-threatening complications associated with disease progression.

Whereas enzyme replacement therapy (ERT) with a human alpha-galactosidase A is the only specific treatment of Fabry disease, there might be an indication for some other treatment modalities too. This includes some preventive measures throughout life as well as some specific interventions in advanced disease (Table I).

Table I: Traditional Symptom Management in Fabry Disease

Lifestyle Changes

Avoidance of stimuli that cause pain, such as stress, physical exertion, heat or sun exposure, and extreme temperature changes.

Increased fluid intake in hot weather and during physical activity to minimise the likelihood of heat exhaustion.

Low fat diet for gastrointestinal symptoms.

“Renal diet” for mild proteinuria.

Avoidance of smoking, since smoking can exacerbate pulmonary symptoms.

Prophylactic Medications

For pain – diphenylhydantion (Dilantin), carbamazepine (Tegretol), Dilantin plus Tegretol, Tegretol plus neurotropin (taken daily); low-dose narcotics.

For stroke prevention – anticoagulants (taken daily), antiplatelets.

For gastrointestinal symptoms – pancrelipase before meals, metoclopramide.

For mitral valve prolapse – antibiotics before surgery or dental procedures.

Renal Complications

Kidney dialysis

Kidney transplantation

Cardiac Complications

Pacemaker insertion for arrhythmia and conduction abnormalities.

Coronary bypass for severe angina.

The choice of complementary treatment modalities next to ERT can also be driven by evidence of disease progression. In general, a cascade of three levels of disease processes can be recognized in Fabry disease (see Table II). The primary processes, directly related to lysosomal storage, can only be treated with ERT. The secondary processes, however, like left ventricular hypertrophy, proteinuria, or a prothrombotic vascular state, might indicate the use of a combined approach: ERT to stop and reverse the primary processes, combined with an ACE-inhibitor or anti-platelet drug to address the secondary processes.

Table II. Natural course – disease processes

In addition, physicians should be sensitive to the psychosocial burden of a chronic, rare, progressive disease. Clinical depression and/or denial are common, as is guilt about passing on the defective gene to children. Family and individual counseling are important resources to offer Fabry patients and their families. Contact with other patients and families struggling with similar issues can help ameliorate feelings of isolation, loneliness, and despair.

The Fabry Registry is an important and useful way for patients and their physicians to contribute to the knowledge and understanding of Fabry disease. This information will be used to develop therapeutic guidelines for treatment and monitoring as well as improving the overall recognition of this rare disease. If you want to enroll Fabry patients in this registry, please contact us.