Fabry disease is an X-linked recessive disorder that leads to the accumulation of a lipid called globotriaosylceramide in the cells of the body. The condition is rare and affects around 1 in 50,000 males. As an X-linked condition, Fabry disease mainly affects males, although females can also be affected.

Although symptoms generally develop during childhood, they can go unrecognized until later on in adulthood when the vital organs are already involved. Since the disease is progressive and can be life threatening, it is important to diagnose Fabry disease as early as possible. Patients with a family history of Fabry disease should be tested for the condition regardless of their symptom profile.

Diagnosis

The steps taken to diagnose this disease are described below.

Presumptive diagnosis

A presumptive diagnosis can be made based on evaluation of the patient’s symptoms. Typical features of this condition include pain in the hands and feet, dark red spots on the skin called angiokeratomas, a decrease in sweat function (hypohidrosis), opaque cornea, hearing loss, gastrointestinal complaints and tinnitus. The patient is also asked about any family history of the condition or symptoms of the condition among other family members.

Biochemical diagnosis

• Enzymatic assay – The globotriaosylceramide accumulation that occurs in Fabry disease is caused by a deficiency in the enzyme α galactosidase A (α-GAL A). In males, the level of α-GAL A activity in the plasma, leukocytes, tears, or tissue can be tested using a synthetic substrate for the enzyme and a diagnosis confirmed by a low or undetectable level of α-GAL A activity. The measurement of α-GAL A is not as useful for confirming a diagnosis in affected females or carriers of the disease because these individuals often have a normal level of α-GAL A activity.

• The α-GAL A deficiency is caused by a mutation in the GLA gene. Most of the mutations that have been identified so far are inherited mutations. Linkage analysis of the GLA gene is the most reliable way of confirming a diagnosis in females.
• Females can also be diagnosed in cases of low or absent α-GAL A activity accompanied by lipid laden biopsied tissue or urinary sediment.