what is it and what are the symptoms

This accumulation is caused by a partial (or total) deficiency of the enzyme α-galactosidase (α-Gal) A, resulting from a mutation of the X chromosome, which causes an accumulation of glycolipids in the tissues and/or an occlusion of the blood vessels 1,2.

The estimated incidence is approximately 1/40,000 men3 and 1/20,000 women4.

Fabry disease is hereditary and can be passed from parents to children

Human cells contain chromosomes, which are thread-like structures that carry genetic information.

Females have two X chromosomes in each cell (each X is inherited from one of their parents), while males have one X chromosome and one Y chromosome (the X chromosome is inherited from the mother, while the Y chromosome is inherited from the father)7 .

The mutated gene responsible for Fabry disease is located on chromosome X8.

Women who carry the mutated gene on only one X chromosome are usually affected by Fabry disease, but have less severe symptoms and manifest later in life than men9.

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Signs and Symptoms of Fabry Disease

Fabry disease presents with various non-specific symptoms involving multiple organs10.

The most common signs and symptoms are 11:

  • hearing problems: ringing in the ears (tinnitus) or hearing loss;
  • impaired sweating, which can cause frequent fever and poor resistance to heat or exercise;
  • abdominal problems such as pain, nausea, vomiting or diarrhoea;
  • fatigue and depression;
  • eye changes such as clouding of the cornea;
  • heart problems;
  • the most serious problems are those affecting the heart, kidneys, nervous system and these can be seen in older patients and in advanced stages of the disease;
  • small, raised, dark red spots on the skin (angiokeratomas);
  • pain and burning in the limbs.

Diagnostic

Many patients are misdiagnosed due to the wide variability in the development of Fabry disease over time1,12.

Early diagnosis is essential to adequately manage the effects of the disease on the main organs affected9.

In men, diagnosis is based on analysis of α-Gal A activity and is confirmed by genetic testing; in females, diagnosis must necessarily be based on genetic testing because α-Gal A activity may be within the normal range1,13.

Treatment: to date, several therapies are available for Fabry disease

It is essential to refer to a Center for Rare Diseases for an appropriate assessment.

Bibliography

Mehta A et al. Definition of Fabry disease: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur J Clin Invest 2004;34:236–42.

Hagege AA et al. Screening patients with hypertrophic cardiomyopathy for Fabry disease using a filter paper test: the FOCUS study. Heart 2011;97:131–6.

Spada M et al. High incidence of late-onset Fabry disease revealed by neonatal screening. Am J Human Genet 2006; 79:31–40.

Meikle PJ et al. Prevalence of lysosomal storage disorders. JAMA 1999;281:249–54

Gal A et al. Towards a consensus in the laboratory diagnosis of Fabry disease – recommendations from a group of European experts. Inherit Metalab Dis 2011; 34:509–514.

Germain DP. General aspects of X-linked diseases. In: Mehta, A. et al (eds). Fabry disease: perspectives from 5 years of FOS. Oxford: OxfordPharmaGenesis; 2006. Chapter 7.

National Human Genome Research Institute (NHGRI) Chromosomes Fact Sheet. Available at: https://www.genome. gov/26524120/chromosomes-fact-sheet/ (Utlimo accesso: 03/26/2018).

Desnick RJ. A-galactosidase A deficiency: Fabry disease. In: Scriver, CR. et al (eds). The metabolic and molecular bases of hereditary diseases. New York: McGraw Hill; 2001: 3733–74.

Mehta A, et al. Fabry disease: a review of current management strategies. QJ Med 2010; 103(9): 641–659.

Ries M, Gal A. Genotype-phenotype correlation in Fabry disease. In: Mehta, A. et al (eds). Fabry disease: perspectives from 5 years of FOS. Oxford: OxfordPharmaGenesis; 2006. Chapter 34.

Germain DP. Fabry disease. Orphanet J Rare Dis 2010; 5:30.

Beck M. In: Mehta A, et al. (eds). Fabry disease: perspectives from 5 years of FOS. Oxford: OxfordPharmaGenesis. 2006; Chapter 16.

Gupta S et al. The relationship between vascular glycolipid storage and clinical manifestations of Fabry disease: a cross-sectional study of a large cohort of clinically affected heterozygous women. Medicine (Baltimore) 2005;84:261–8.

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