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Fabry Disease
Why Should I Suspect Fabry Disease in Children?
a report by
Björn Hoffmann and Ertan Mayatepek
Department of General Paediatrics, University Children’s Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf
For more than a century Fabry disease was regarded as a rare condition to 16 years of age present with these skin alterations,
5
which led
affecting between one in 47,000 and one in 117,000 male individuals.
1,2
Johannes Fabry, a German dermatologist, to name the disease
Spada et al. recently reported on the results of newborn screening in Fabry ‘angiokeratoma corporis diffusum’.
6
Typical locations are include the
disease.
3
Analysing dried blood spots from patients in northern Italy, they fingertips, peri-umbilical region and the ‘bathing trunk’ area. A less
found a presumable prevalence of about one in 3,100 male neonates. obvious but possible affected site may be the intestinal tract mucosa.
5
Based on the population of all of the countries in the EU (approximately As a consequence of impaired autonomic skin nerve function in Fabry
490 million people), this would lead to more than 150,000 individuals disease, sweating may also be disturbed.
7
Hypohidrosis is most often
affected with Fabry disease in the EU. In the two available patient seen (>33% of patients); however, anhidrosis and even hyperhidrosis
registries, the Fabry Outcome Survey (FOS) and the Fabry Registry, fewer have also been reported. Temperature insensitivity may also be
than 4,000 patients with confirmed Fabry disease were registered in 2008. indicative of Fabry disease.
5
The results of Spada et al. indicate the need to confirm the incidence of
the condition, as it is possible that the prevalence may be different in other Nervous System
populations too. It is possible that Fabry disease is not as rare as has been Patients with Fabry disease may complain about both acute pain crises
accepted in the past, and a substantial number of patients with Fabry and chronic pain episodes, with more than 70% of patients with Fabry
disease in the EU are yet to be diagnosed and lack causal treatment. disease affected with a reported mean age at onset of pain of 14 years
Focusing on the clinical manifestations of Fabry disease in childhood and in males and 19 years in females.
8
Most often, pain is of a burning or
adolescence may lack both comprehensiveness and completeness. tingling character and termed ‘acroparaesthesia’. Analyses of large
Regardless of the particularities of adult patients with Fabry disease, one cohorts of patients revealed that the whole body may be affected.
has to consider that patients with typical symptoms of Fabry disease may Some patients report aggravation of the pain during physical activity,
show up every day in paediatric outpatient clinics and inpatient elevated ambient or body temperature and the consumption of certain
departments, specialised or not. In order to ‘unmask’ the disease from foods. Storage material in dermal axons has been identified as the
the broad variety of potential differential diagnoses there is a need for an pathological correlate. Thin myelinated C-fibres are more severely
increasing awareness of Fabry disease and its symptoms, along with clear affected by Gb3 storage than thick unmyelinated Aδ-fibres.
9
strategies for its diagnosis. If the disease has been confirmed in suspected
individuals, effective treatment has to be initiated. Gastrointestinal Tract
Gastrointestinal symptoms are reported in more than 50% of patients
Underlying Pathology with Fabry disease, with the most prevalent gastrointestinal complaint
The biochemical basis of Fabry disease is the deficiency of the enzyme being abdominal pain.
10
It is reported more frequently in children than in
α-galactosidase-A. Belonging to the group of acid hydrolases that are adults, and at 14 years the mean age of reported onset of abdominal
found in the lysosomes of most human cells, α-galactosidase-A takes pain is similar to that of acroparaesthesia. Diarrhoea and constipation are
part in the cleavage of biological macro-molecules that assault during frequently reported in Fabry disease. There are no signs of inflammation,
regular cell turnover.
4
Lack of the enzyme leads to an accumulation of a prolonged gastrointestinal transit time and a feeling of early satiety, and
globotriaosylceramide (Gb3) in cells, tissues and body fluids and, as a these complaints mirror the picture of irritable bowel syndrome.
consequence, cellular and organ function is impaired. Symptoms may Pathology studies found storage material in intestinal neurons, smooth-
occur early in life and become progressively severe with age. Fabry muscle cells and endothelial cells.
11–13
disease is inherited in an X-linked trait. However, females may develop
the whole spectrum and burden of disease, too. Kidney
Up to 56% of children below 18 years of age have been shown to develop
Everyday Symptoms in Childhood Fabry Disease proteinuria,
14,15
and there are also case reports about children two years of
Table 1 summarises the clinical symptoms of Fabry disease according age suffering from Fabry disease and proteinuria. Progressive renal
to the typical age at which they may have their onset. insufficiency may occur with increasing age, and renal failure has been
reported to develop as early as 16 years of age.
16
Töndel et al. found
Skin accumulated Gb3 in podocytes, with glomerula and tubulointerstitial cells
Angiokeratoma may occur ‘single-standing’ or as multiple pinhead- prior to clinical kidney impairment in seven out of nine children with Fabry
sized, red-brownish dilated skin vessels. When initially viewed, one may disease during kidney biopsy.
17
Glomerular endothelial cell inclusions were
consider angiokeratoma as freckles; however, they often disappear also found in the same number of children; the remaining two patients
when pressure is applied to them. Thirty to forty per cent of children up were already on enzyme replacement therapy (ERT).
© TOUCH BRIEFINGS 2008 21
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