Fabry Disease (aka Anderson-Fabry Disease, Alpha-galactosidase A deficiency)

Specimen

Blood spot card using an EDTA blood sample made in the laboratory. A minimum of 2 fully filled blood spots

Follow-up, confirmatory testing in plasma and leucocyte analysis is required in low enzyme activity, these requests should be made via the Genomics department.

Test Usage

Fabry disease in an X-linked in-born error of metabolism known as sphingolipidoses, a subgroup of lysosomal storage disorders.  Incidence is estimated to be estimated 1 in 40,000 to 60,000 males. Heterozygous females may also be symptomatic.

Globotriaosylceramide (aka CD77/Gb3 or ceramide trihexoside), is a sugar-fat compound which accumulates in the body’s cells, due to the deficiency of the alpha-galactosidase A enzyme (α-galactosidase A).

Accumulation of globotriaosylceramide begins in childhood, and intra-lysosomal deposition leads to characteristic features of Fabry disease, including:

• episodic pain (particularly in the hands and feet called acroparesthesias)
• angiokeratomas
• hypohidrosis
• corneal clouding
• gastrointestinal effects
• progressive kidney damage
• cardiac manifestations (left ventricular hypertrophy, mitral insufficiency, ascending aortic dilatation, coronary artery disease and conduction abnormalities leading to congestive heart failure, arrhythmias and MI)
• Cerebrovascular manifestations (early stroke, transient ischaemic attacks, white matter lesions, hemiparesis, tinnitus and hearing loss)

Clinical manifestations in heterozygous females may range from asymptomatic to as severe as affected males, but typically with global later onset and slower progression.

A cardiac variant presents with cardiomegaly and mild proteinuria after 40 years of age.

In affected males with classic or variant phenotypes, the disease is identified by demonstrating an α-galactosidase A enzyme deficiency in leukocytes. Further confirmatory testing is NOT required in males if enzyme activity is normal.

Heterozygous females may have normal to low enzyme activity levels, therefore further confirmatory DNA analysis is required.

Availability

Referred Test

Turnaround Time

4 weeks

Cannot be added on to an existing request