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Table 1: Clinical Symptoms of Fabry Disease According to
further biochemical diagnostic procedures. To confirm or exclude Fabry
Age at Onset
disease in male patients determination of residual α-galactosidase-A
activity in leucocytes may be used. In female patients confirmation of
a pathogenic mutation in the GLA-gene is mandatory. Randomised
X-inactivation determination of impaired enzyme activity may reveal false-
Abdominal pain, diarrhoea, constipation
positive and/or false-negative results.
Left ventricular hypertrophy, heart-rate variability
Adulthood Corneal clouding Identifying Fabry disease in one patient does not mean the end of
Hearing impairment, tinnitus
diagnostic procedures. Because of the X-linked inheritance, it is
Dyspnoea, heart failure, angina, palpitations
important to perform a pedigree analysis and refer the patient and/or
Progressive renal insufficiency
the family for genetic advice. The significance of this procedure is
Transient ischaemic attacks, stroke
proved by the fact that most paediatric patients in the Fabry Outcome
Survey have been identified through pedigree analyses.
Table 2: Five Questions to Help Unmask Fabry Disease
1. Do you sweat less than others or do you not sweat at all?
Causal Treatment of Fabry Disease
For decades the treatment of Fabry disease has been symptomatic only
Do you have difficulties standing upright in warm weather?
and affected by a lack of perspective. Modern pharmacogenetic methods
and/or have allowed for the reproduction of human α-galactosidase as a
Are you sensitive to cold temperatures?
pharmaceutical preparation. Two of these formulations are available
2. Have you been excused from sports lessons in school?
within the EU: agalsidase-alpha and agalsidase-beta. Administration of
either of these drugs has to be performed every second week as an
Have you been off school because of unexplained gastrointestinal complaints?
intravenous infusion. The safety and efficacy of these preparations has
3. Does your family have a history of kidney disease and/or cardiac disease before
55 years of age?
been demonstrated in several studies. In adult patients an improvement of
4. Are there unexplained deaths or deaths before 60 years of age in your family?
and kidney function,
5. Do you need pain medication on a regular basis? quality of life
has been reported. Less information has been gained on
the effects of ERT in children. This may, in part, be due to the relatively
Heart small number of patients in this age group identified so far. Despite these
Typical left ventricular hypertrophy (LVH) in Fabry disease is not only a considerable improvements in patients receiving ERT, it is unclear whether
problem in adulthood, but may also occur in children. Kampmann et al. treatment may also be able to improve life expectancy. In the face of the
found manifest LVH in seven of 20 children (35%).
All of the children limited funding and financial problems of healthcare systems in most
had a left ventricular mass above the 75th percentile, and functional countries, the unclear long-term advantages of ERT are often brought up
impairment of the left ventricle has been observed before thickening of by healthcare insurance companies, particularly before the institution of
the myocardium. Another non-invasive measure of cardiac involvement in ERT in a patient. Costs can easily reach €250,000 per year, extrapolated
childhood Fabry disease is the variability of heart frequency, particularly on a 70kg patient (~€3,500 kg bodyweight). Since treatment has to be
Variations of heart frequency allow the cardiac muscle to rest; conducted on a lifelong basis, the financial burden on a healthcare system
impaired heart-rate variability is an indicator of permanent cardiac is obvious. Nevertheless, to prevent continuous and progressive organ
exertion and has been demonstrated to be a risk factor for sudden damage it is essential to start treatment before irreversible organ damage
cardiac death in adult patients with other diseases.
Post mortem has taken place, and an early diagnosis is essential.
analyses and in vivo studies have demonstrated storage material in
myocardial cells and cells of the electrical conduction system. Conclusions
Fabry disease is a condition with very common symptoms. There is good
Unmasking Fabry Disease evidence that a considerable proportion of patients remain undiagnosed.
Early manifestations of Fabry disease are non-specific and allow for Paediatricians may see symptoms of Fabry disease every day. Treatment
numerous differential diagnoses. Table 2 summarises questions that may of Fabry disease is both safe and effective, and diagnosis in childhood
be helpful to identify the disease in the maze of differential diagnoses. If along with the timely initiation of sufficient treatment seems to be the
the answer to two or more of these questions is ‘yes’, there is a need for only chance of preventing irreversible organ damage. ■
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