Fabry Disease – A rare lysosomal storage disorder

About the disease

Fabry disease (sometimes called Anderson-Fabry disease) was first described in 1898 by two dermatologists working independently in Germany and England: Johannes Fabry (1860-1930) and William Anderson (1842-1900).

Fabry Disease is an inherited genetic lysosomal storage disorder. The defective gene is recessive and located on the X-Chromosome.

Patients produce insufficient amounts of - or completely lack - alpha-galactosidase A (also alpha-GAL or ceramidetrihexosidase), an enzyme, which is essential for catabolizing glycosphingolipids, especially globotriaosylceramide (GL-3). In effect, GL-3 accumulates in blood vessels, as well as in numerous tissues and organs, such as heart, kidneys, and eyes.

The disease predominantly affects males. About 1 in 40,000 men is estimated to be Fabry positive. Recent studies suggest that these figures might actually underestimate prevalence of the disease and that rather 1 in 3,100 males is affected by the disorder. In the general population prevalence is estimated to be 1 in 117,000.

Symptoms

Patients with Fabry disease usually develop one or more of the following symptoms:

• Pain in feet, hands, joints (acroparesthesia)
• Reduced sweating (hypohidrosis) and easy overheating
• Skin conditions, rashes (predominantly angiokeratomas)
• Cardiac complications (i.e. ventricular hypertrophy, coronary artery disease)
• Renal  problems (impaired function, failure)
• Neurological abnormalities (i.e. headache, hemiparesis)
• Cerebrovascular problems (especially premature stroke)
• Gastroenterological problems (i.e. recurring diarrhea)
• Corneal and lenticular opacity (i.e. whorled corneal)

Diagnostic challenges

Since Fabry disease is little known, clinically heterogeneous symptoms can be misleading and cause wrong diagnoses. Fabry patients often go through years of false diagnoses and treatments before the disease is identified.

Apart from irreparable damage inflicted on tissue and organs, late diagnosis has severe negative effects on the patient’s psychological health. Oftentimes, Fabry patients encounter isolation and stigmatization as suspected “malingerers”.

Presumptive diagnosis in men can be verified by an enzyme test, which analyzes alpha-GAL levels in blood or tissue. Due to x-chromosomal inactivation, enzyme tests may return negative results for Fabry positive women. Therefore, a genetic test should be considered as diagnosis tool.

Therapy

Since August 2001, effective Enzyme Replacement Therapy (ERT) exists. Especially if started at an early stage of the disease, ERT can stop or even reverse accumulation of glycosphingolipids and therefore, reduce damaging effects on tissue and organs.