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 a resultant abnormal accumulation of globotriaosylceramide (Gb3) in various organ systems. In men, the condition is fatal within 50 years without treatment. Heterozygous women, in addition to being carriers, may also exhibit similar symptoms as men.
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 be 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 involvement begins with proteinuria progressing to end stage renal failure usually in the 4th 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).
Fabry disease is affiliated with corneal verticillata and lenticular abnormalities. Recent studies have proposed eye signs in Fabry disease in association with α-galactosidase A mutations could be an indicator of disease severity 7.
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.
Avascular necrosis of the femoral head has been described.
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).
Inborn errors of metabolism
- disorders of carbohydrate metabolism
- disorders of amino acid metabolism
disorders of the urea cycle
- carbamoyl phosphate synthetase I deficiency
- ornithine transcarbamylase deficiency (OTCD)
- disorders of organic acid metabolism
- disorders of fatty acid oxidation and mitochondrial metabolism
- disorders of porphyrin metabolism
- disorders of purine or pyrimidine metabolism
- disorders of steroid metabolism
- disorders of mitochondrial function
- disorders of peroxisomal function
lysosomal storage disorders
- activator Deficiency/GM2 Gangliosidosis
- cholesteryl ester storage disease
- chronic hexosaminidase A Deficiency
- Danon disease
- Fabry disease
- Farber disease
- Gaucher disease
- GM1 gangliosidosis
- I-Cell disease/Mucolipidosis II
- infantile free sialic acid storage disease
- juvenile hexosaminidase A deficiency
- Krabbe disease
- lysosomal acid lipase deficiency
- metachromatic Leukodystrophy
- multiple sulfatase deficiency
- Niemann-Pick disease
- meuronal ceroid lipofuscinoses
- CLN6 disease
- Finnish Variant Late Infantile CLN5
- Jansky-Bielschowsky disease
- Kufs disease
- northern epilepsy
- Santavuori-Haltia disease
- Pompe disease
- Sandhoff disease
- Schindler disease
- Salla disease
- Tay-Sachs disease
- Wolman disease
Toxic and metabolic encephalopathies
- overview by region
- white matter
- grey matter
- by agent/substance
- by systemic illness
- overview by region
- by substance
- Wernicke encephalopathy (vitamin B1)
- by substance
- Kearns-Sayre syndrome
- Leigh syndrome
- mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS)
- myoclonus epilepsy with ragged red fibres (MERRF)
- mitochondrial deletion syndromes
- progressive cerebral poliodystrophy (also known as Alpers syndrome)
- trichopoliodystrophy (also known as Menkes disease)
- 1. Lidove O, Klein I, Lelièvre JD et-al. Imaging features of Fabry disease. AJR Am J Roentgenol. 2006;186 (4): 1184-91. doi:10.2214/AJR.05.0019 - Pubmed citation
- 2. De Cobelli F, Esposito A, Belloni E et-al. Delayed-enhanced cardiac MRI for differentiation of Fabry's disease from symmetric hypertrophic cardiomyopathy. AJR Am J Roentgenol. 2009;192 (3): W97-102. doi:10.2214/AJR.08.1201 - Pubmed citation
- 3. Moore DF, Ye F, Schiffmann R et-al. Increased signal intensity in the pulvinar on T1-weighted images: a pathognomonic MR imaging sign of Fabry disease. AJNR Am J Neuroradiol. 2003;24 (6): 1096-101. Pubmed citation
- 4. Linhart A, Kampmann C, Zamorano JL et-al. Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey. Eur. Heart J. 2007;28 (10): 1228-35. doi:10.1093/eurheartj/ehm153 - Pubmed citation
- 5. Kolodny EH, Pastores GM. Anderson-Fabry disease: extrarenal, neurologic manifestations. J. Am. Soc. Nephrol. 2002;13 Suppl 2 (suppl 2): S150-3. J. Am. Soc. Nephrol. (full text) - Pubmed citation
- 6. Mehta A, Hughes DA. Fabry Disease. 2002 Aug 5 [Updated 2013 Oct 17]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1292/
- 7. Pitz S, Kalkum G, Arash L, Karabul N, Sodi A, Larroque S, Beck M, Gal A. Ocular signs correlate well with disease severity and genotype in Fabry disease. PloS one. 10 (3): e0120814. doi:10.1371/journal.pone.0120814 - Pubmed