Clinical manifestations of Fabry disease in children: data from the Fabry Outcome Survey.
BACKGROUND
Fabry disease is a rare X-linked disorder caused by deficient activity of the enzyme alpha-galactosidase A. This produces progressive lysosomal accumulation of globotriaosylceramide throughout the body, leading to organ failure and premature death.


OBJECTIVE
Here, we present the clinical manifestations of Fabry disease in children enrolled in FOS--the Fabry Outcome Survey--a European database of the natural history of Fabry disease and the effects of enzyme replacement therapy with agalsidase alfa (Replagal).


METHODS
Currently, there are 545 patients in FOS, from 11 European countries. We analysed the baseline demographic and clinical characteristics of 82 of these patients (40 boys, 42 girls) who were below 18 y of age. The median age at evaluation (defined as the median age at entry into FOS) was 12.5 and 13.2 y for boys and girls, respectively.


RESULTS
The most frequent early clinical manifestations of Fabry disease were neurological (acroparaesthesiae, altered temperature sensitivity) and gastrointestinal symptoms (altered bowel habits and abdominal pain), which were documented in about 80% and 60% of patients, respectively, at the time of evaluation and subsequent entry into FOS. Tinnitus, vertigo, fatigue and angiokeratoma were present in over 40% of patients. Symptoms were noted in early childhood and occurred with similar frequency in boys and girls, although the onset of symptoms was 2-5 y later in girls than in boys. There was an approximately 3-y delay from onset of symptoms to diagnosis, and patients were frequently misdiagnosed.


CONCLUSIONS
Although the life-threatening complications of Fabry disease, such as stroke and renal and heart failure, are not seen in children, the present analysis shows that other symptoms are common and may have an impact on quality of life.
Department of Paediatric Endocrinology, Diabetes and Metabolism, Addenbrooke's Hospital, Cambridge, UK. uma.ramaswami@addenbrookes.nhs.uk
Uma
U
Ramaswami
Catharina
C
Whybra
Rosella
R
Parini
Guillem
G
Pintos-Morell
Atul
A
Mehta
Gere
G
Sunder-Plassmann
Urs
U
Widmer
Michael
M
Beck
D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D000795:Fabry Disease / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007527:Isoenzymes / Q000627:therapeutic use; D008297:Male; D017063:Outcome Assessment, Health Care; D011994:Recombinant Proteins; D000519:alpha-Galactosidase / Q000378:metabolism / Q000627:therapeutic use
D007527:Isoenzymes; D011994:Recombinant Proteins; C000627036:agalsidase alfa; D000519:alpha-Galactosidase