Fabry Disease: An Overview

Written by: Abigail Sayers

Fabry disease is classified as a lysosomal storage disease and can be caused by multiple types of pathogenic changes in the gene GLA. GLA is located on the X chromosome and can be altered through deletions, insertions, missense or nonsense mutations, splice-site anomalies, and reassortment of the DNA. Fabry disease causes progressive damage to the heart, kidneys, skin, eyes, central nervous system, and gastrointestinal system, which can eventually lead to organ failure (16).

Fabry disease affects molecular structures within each cell called the lysosomes, which function by digesting foreign, or damaged materials, like viruses, bacteria, and old cell parts (15). GLA encodes for the α-GAL enzyme that digests globotriaosylceramide (Gb3) into galactose. When the gene stops functioning the α-GAL enzyme globotriaosylceramide (Gb3) is not produced and Gb3 accumulates within cellular lysosomes.

Symptoms of Fabry Disease

Written by: Shirah Segal

Variants in the GLA gene prevent the enzyme from working properly, leading to a buildup of globotriaosylceramide and subsequent cell damage (38). Symptoms of Fabry disease begin in childhood and include episodes of numbness, tingling, and pain, small red spots on the skin, decreased ability to sweat, cloudiness in the eye, gastrointestinal symptoms, and hearing difficulties. Over time, more serious complications can develop, including kidney failure, heart failure, and stroke. There are two forms of Fabry disease, which are classified by the age of onset. In the classic form, symptoms appear in early childhood and progressively worsen. In the late-onset form, symptoms do not appear until the 30s or later (38, 39). 

Unlike most other X-linked conditions, females who have Fabry disease often display symptoms. Females may experience nervous system abnormalities, kidney problems, and chronic fatigue. These symptoms may appear later in life and are typically milder than those seen in males (38, 39). 

Reviewed and Edited by Rachel Baer, MSc, and Andy McCarty, MS, LGC, CGC

Learn More About Genetics:

• Sample Types

• Prenatal and Fetal Testing

• Aneuploidies

• Cytogenetics

Learn More About the X Chromosome:

• The X Chromosome

• X and Y Chromosomal Aneuploidies

• DMD and BMD

• Hemophilia A

• Alport Syndrome

• Fragile X Syndrome

• X-Linked Charcot-Marie-Tooth (CMTX)