Pulmonary Disease and Exercise Tolerance in Boys With Fabry Disease
Pulmonary Disease and Exercise Tolerance in Boys With Fabry Disease
When to start children with Fabry disease on therapy is controversial because of its expense
 and inconvenience. Many Fabry children complain of exercise intolerance. In adults, the
 investigators have found decreased lung function and ability to exercise on a treadmill.
 Whether or not lung function and exercise capacity is abnormal in children is unknown. While
 lung function and exercise tests are commonly part of routine evaluations for adults with
 Fabry, they are not yet for children.

 The objective of the proposed study is to more accurately define the lung and exercise
 abnormalities in a group of 20 boys from 8-18 years of age with Fabry disease who have not
 been treated with enzyme replacement therapy (Fabrazyme).
Fabry disease is due to an alteration in the genetic material (DNA) that causes a deficiency
 of the alpha-galactosidase A enzyme. This enzyme aids in the breakdown and elimination of
 certain types of fatty substances called glycolipids. These glycolipids are normally present
 within the body in most cells. When alpha-galactosidase A is lacking, these glycolipids build
 up in various tissues such as the eye, liver, kidney, skin, muscle, heart, and blood vessels.
 The build up of glycolipid levels in these tissues, particularly globotriaosylceramide
 (GL-3), is thought to cause the clinical symptoms that are associated with Fabry disease.
 Fabry disease causes chronic kidney damage leading to a need for dialysis or kidney
 transplantation, chronic heart damage leading to abnormal heart rhythms and heart attacks and
 strokes at an early age, nervous system damage leading to chronic pain, and a premature
 death. Because the gene for Fabry is on the X chromosome (men have only one X chromosome
 while women have two), most patients with symptoms of Fabry are men but many women have
 symptoms that may be as severe as men. There is currently a FDA approved treatment available
 that treats many of the symptoms of Fabry, but it involves intravenous infusions every other
 week and is very expensive.

 When to start children on therapy is controversial because of its expense and inconvenience.
 Children with significant pain or gastrointestinal problems are started on therapy
 immediately, otherwise not until they are at least teenagers. Increasing evidence suggests
 that even without overt symptoms, significant, irreversible damage may be occurring in
 childhood. However, determining whether such damage is present or not requires biopsies.
 There are no simple measures of disease severity.

 Many Fabry children complain of exercise intolerance. In adults, the investigators have found
 decreased lung function and ability to exercise on a treadmill. Whether or not lung function
 and exercise capacity is abnormal in children is unknown. While lung function and exercise
 tests are commonly part of routine evaluations for adults with Fabry, they are not yet for
 children.

 The objective of the proposed study is to more accurately define the lung and exercise
 abnormalities in a group of 20 boys from 8-18 years of age with Fabry disease who have not
 been treated with enzyme replacement therapy (Fabrazyme). This will be done by several
 breathing tests and exercising on a treadmill. If the breathing tests are abnormal, then
 testing would serve as an easy way to evaluate children and help decide when therapy should
 be started and monitor the effectiveness of therapy.

 Each person that consents to participate in the study will be required to commit to a single
 study visit that will last approximately 4 hours at Cedars-Sinai Medical Center. The
 participant will be expected to wear loose fit clothing and comfortable athletic footwear.

 As part of the research, participants will be asked to participate in the following tests:

 1. A pulmonary function test

 2. Exercise test. Results will be forwarded to each participant's primary care physician.

 All subjects must have previously been enrolled in the Fabry Registry and have the
 recommended standard of care assessments in order to be eligible for this pilot study.
Inclusion Criteria:

 -  Fabry disease

 -  Male

 -  Between 8-18 years of age

 -  Enrolled in Fabry registry and have standard assessments

 Exclusion Criteria:

 -  Enzyme replacement therapy or an experimental therapy

 -  Inability to perform the tests

 -  Other, serious medical conditions that would impact the tests