Background
Fabry disease is a hereditary, X-linked lysosomal storage disorder caused by inherited genetic mutations in the GLA gene, resulting in deficient activity of the enzyme alpha-galactosidase A (a-gal A). Deficiency of this enzyme results in the accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3) in various cells and tissues throughout the body including the walls of small blood vessels, nerves, dorsal root ganglia, renal glomerular and tubular epithelial cells, and cardiomyocytes. This accumulation leads to a complex, progressive, multisystem condition affecting several major organs including the kidneys, heart, nervous system and skin. The clinical manifestations are summarized in Table 1 and frequently include: chronic pain and acroparasthesia, gastrointestinal disturbances, characteristic skin lesions (angiokeratoma), progressive renal impairment, cardiomyopathy, and stroke (Clarke et al 2007).
Table 1: Clinical Features of Fabry Disease
| Affected organ system/domain |
Features |
| Heart |
- Left ventricular hypertrophy and dysfunction
- Valvular dysfunction
- Conduction and flow abnormalities
- Disturbed heart rate variability
|
| Kidney |
Progressive decline in renal function including:
- microalbuminuria/proteinuria
- decreased glomerular filtration rate
- elevated serum creatinine levels
- isothenuria
- end-stage renal failure
|
| Central nervous system |
- Changes to the cerebral circulation
- White matter lesions
- Transient ischaemic attacks
- Stroke
|
| Peripheral nervous system |
- Neuropathic pain – acroparesthesia, painful febrile crises
- Hypohidrosis/anhidrosis (rarely hyperhidrosis)
- Telangiectasia
|
| Gastrointestinal system |
- Abdominal pain
- Diarrhea
- Nausea
- Bloating
|
| Skin |
- Angiokeratoma
- Acromegaly-like facies
- Lymphoedema
|
| Eye |
- Cornea verticillata
- Tortuosity of conjunctival and retinal vessels
- Lens opacities (capsular or subcapsular cataracts)
|
| Ear |
- Vertigo
- Tinnitus
- Progressive, or occasionally sudden, hearing loss
|
| Neuropsychiatric and psychosocial |
- Impaired quality of life
- Depression
- Impaired memory, attention and motor function
|
| Other |
- Mild-to-severe airway obstruction
- Anemia
- Osteopenia
- Thyroid dysfunction
|
The clinical presentation of Fabry disease is heterogeneous and the natural history is incomplete. Lifespan is typically reduced in patients by approximately 20 years in males and 15 years in females compared with the general population. Death is usually due to heart disease, kidney failure, or stroke (MacDermot et al 2001; MacDermot et al 2001).
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