Fabry disease is a rare lysosomal storage disease of X-linked recessive inheritance, which was first described in Germany and the United Kingdom in 1898 [1,11,50]. Due to mutations in the GLA gene, located on the X chromosome (Xq22.1), patients show a partial or complete deficiency of ceramidtrihexosidase, also referred to as α-galactosidase A (α-Gal A) [3,50]. The biochemical aetiology of this condition was discovered several years later [4,22]. Because of this mutation, sphingolipids accumulate in various tissues. Particu¬larly globotriaosylceramide (Gb3) accumulates in skin, eye, heart, kidney, brain, vascular and nervous systems . Accordingly, Fabry disease is a multisystem disease.
The disease can be divided into a severe, classical phenotype and a generally milder non-classical phenotype. In the severe form, there is typically no residual enzyme activity . The non-classical type, also referred to as late-onset or atypical Fabry disease, often demon¬strates a more variable disease severity and progression. Disease manifestations are often limited to a single organ with mainly isolated renal or cardiac manifestation . Males tend to develop greater disease severity than females . Skewed X inactivation might be responsible for the variability of the phenotype in women [3,10].
The overall incidence in new-born children varies between 1/40,000 or 1/117,000 in men up to much higher incidences with about 1/3100 to 1/1000 in high-risk populations, and even 1:875 in male and 1:399 female live births in Taiwan. It seems to differ between various countries [8,18,29,30,42,45].
In a cohort of 98 male patients, the mean age of diagnosis was 21.9 years . The mean median cumulative survival seems to be 50 ± 8 years for males and up to 72 years for females. [5,27,46] The disease may present at any age and generally is progressive .
The diagnosis can be difficult, because patients present with nonspecific complaints such as headaches, limb or abdominal pain plus diarrhoea. The definitive diagnosis is most commonly made following severe complications such as stroke, heart and kidney failure .
Typical facial features include periorbital fullness, prominent lobules of the ears, bushy eye-brows, recessed forehead, pronounced or prominent nasal angle, generous nose or bulbous nasal tip, prominent supraorbital ridges, shallow midface, full lips, prominent nasal bridge, broad alar base, coarse features, posteriorly rotated ears and prognathism . Other features include short fingers, prominent superficial vessels of hands, 5th digit brachydactyly or clinodactyly .