Fabry Disease

Fabry disease is a rare, inherited disorder that is progressive in nature and affects many of the body’s systems. It is one of about 50 diseases classified as lysosomal storage disorders (LSD), in which a genetic variation disrupts the normal activity of lysosomes in human cells.

What are lysosomes and what do they do?

Lysosomes in human cells contain specific proteins known as enzymes that are responsible for breaking down and recycling molecules such as fats and sugars. Individuals with a lysosomal storage disorder lack one of these necessary enzymes, or do not contain one of these enzymes in sufficient quantities for cells to function properly.

Fabry disease is caused by a mutation in a gene called GLA, which provides instructions for making an enzyme known as alpha-galactosidase A. Lysosomes require this enzyme to properly break down large fat molecules inside the body’s cells.

Fabry disease is a genetic condition. Affected children have a mutated gene on the X chromosome, one of two sex chromosomes contained in each cell. In males, who have a single X chromosome in addition to a Y chromosome in each of their cells, a defective copy of the GLA gene is sufficient to cause Fabry disease. In females, who have two X chromosomes, a defective copy of the GLA gene on both of their X chromosomes will manifest as Fabry disease. The combination of a typical GLA gene on one X chromosome and a mutated GLA gene on the other X chromosome in females may result in less severe symptoms of Fabry disease. In rare cases, a female with one mutated GLA gene may have no signs or symptoms of Fabry disease. These women are called carriers, meaning their children can inherit the condition even though they have no visible symptoms.

Signs and symptoms some children with Fabry disease may experience include:

• Episodes of pain in the hands and feet (acroparesthesias)
• Dark red spots on the skin (angiokeratomas)
• Decreased ability to sweat (hypohidrosis)
• Cloudiness in the front part of the eye (corneal opacity)
• Stomach problems
• Ringing in the ears (tinnitus)
• Hearing loss
• Kidney damage
• Heart complications
• Stroke

Current approaches to Fabry disease are tailored to specific patients and may include enzyme replacement therapy (ERT), targeted symptom management and medication designed to increase alpha-galactosidase activity. Management plans require interdisciplinary collaboration and depend greatly on a patient’s specific disease presentation, age, and a variety of additional factors.

At the Lysosomal Storage Disorder (BoLD) Program, our team of providers is committed to the care of complex patients. As part of Boston Children’s Hospital, we are prepared to meet the challenge of providing multifaceted care by partnering with you and your child to deliver direct care in our BoLD clinic. We work with the broad array of world-class specialists at Boston Children’s to optimize the care we provide your child with Fabry disease.