Fabry Disease: Alpha-galactosidase Enzyme Analysis

Clinical Information

Fabry disease is a lysosomal storage disorder in which absent or reduced production of alpha-galactosidase A leads to the systemic accumulation of globotriaoslyceramide. Total absence of enzyme production results in the more severe, classic form of Fabry disease, while reduced production of alpha-galactosidase A typically often involves milder symptoms that appear later in life. Episodic pain, angiokeratosis, and hypohydrosis are frequently seen in patients with Fabry disease as well as corneal clouding and hearing loss. Gastrointestinal issues and breathing problems are common, and complications including cardiac abnormalities, kidney disease, and strokes can be life-threatening. Although Fabry disease is an X-linked disorder that primarily affects males, carrier females may become symptomatic. This condition occurs in approximately 1 in 55,000 males, and the development of enzyme replacement therapy has greatly improved the prognosis for many patients.

Technical Information

Alpha-galactosidase enzyme activity is measured using 4-methylumbelliferyl (4-MU) substrate (leukocytes, plasma, fibroblasts) or liquid chromatography-tandem mass spectrometry (LC-MS/MS) (DBS).

Specimen Requirements

• Accepted sample types for this test include dried blood spots (DBS), fibroblasts, leukocytes, and plasma.
• DBS: Approximately 75 uL of blood should be applied to each of the five circles on filter paper dried blood spot card. Allow blood to dry for at least 4 hours before shipping.
• Fibroblasts: Tissue sample should be stored in sterile culture media; cultured fibroblasts should be sent in two T25 flasks. Do NOT place tissue in formalin or formaldehyde. Do not freeze tissue.
• Leukocytes: A minimum of 5 mL whole blood (7-10 mL preferred) collected in a sodium heparin tube
• Plasma: A minimum of 3 mL whole blood collected in a sodium heparin tube; or blood can be centrifuged and a minimum of 1 mL plasma removed and sent for analysis.

Transport Instructions

• DBS: Ship DBS card at ambient temperature.
• Fibroblasts: Ship tissue sample or cultured fibroblasts at ambient temperature
• Leukocytes: Whole blood should be shipped at ambient temperature. If leukocytes are being isolated at another laboratory, the pellet should be frozen after specimen processing and shipped frozen on dry ice.
• Plasma: Plasma should be frozen after collection and shipped frozen, preferably on dry ice. Whole blood should be shipped at ambient temperature.