Fabry disease

Fabry disease is a multisystem disorder which results from an X-linked inborn error of metabolism. The disease is characterised by a deficiency in hydrolase alpha-galactosidase activity with resultant abnormal accumulation of globotriaosylceramide (Gb3) in various organ systems. In men the condition is fatal within 50 years without treatment. Heterozygous women addition to being carriers may also exhibit similar symptoms as men. 

Clinical presentation

Neurological

Small vessel ischaemia is the main mechanism of central nervous system manifestations, with ischaemic strokes, especially of the posterior circulation being common. Multi-infarct dementia can ensue, although MRI T2 hyperintensities in the white matter of the frontal and parietal lobes can been seen in asymptomatic patients. MRI is used to monitor treatment response. 

T1 weighted images also demonstrate high signal in the deep grey matter especially that of the pulvinar, relating to mineralisation (see basal ganglia T1 hyperintensity). Exclusive involvement of pulvinar is thought to be characteristic of the condition ⁴.

Both T2 and T1 changes have been seen to regress with treatment if instituted early enough. 

Acroparesthesia is a common manifestation, more so than ischaemic changes described above, and can be debilitating ⁶. 

Autonomic (sympathetic) nervous system involvement can lead to gastrointestinal autonomic dysfunction. 

Renal

Renal involvement begins with proteinuria progressing to end stage renal failure usually in the 4^th decade. On imaging the kidneys have non specific findings of medical renal disease including increased echogenicity, thinned renal cortex and multiple renal cysts. The cysts are perhaps the most specific sign, typically small and of uniform size, located just beneath the capsule, aiding in differentiating these from autosomal dominant polycystic kidney disease (ADPKD). 

Ocular

Corneal and lenticular abnormalities

Cardiac

Focal myocardial fibrosis leads to left ventricular hypertrophy. Thickening of the aortoventricular valve is seen in 25% of patients. Mitral valve disease with thickening and regurgitation is also demonstrated. 

Musculoskeletal

Avascular necrosis of the femoral head has been described. 

Pulmonary

There can be chronic obstructive airways disease like symptoms with bronchial wall thickening. 

Treatment and prognosis

Enzyme substitution (hydroxylase alpha-galactosidase) is efficacious in rectifying the metabolic deficit. 

History and etymology

First described in 1898 by Johanne Fabry,German dermatologist (1860 -1930).