How Rheumatologists Can Help

Rheumatologists can play a critical role in the detection of Fabry disease. By recognizing the early signs and symptoms, rheumatologists have the opportunity to identify Fabry disease earlier in the disease course. A geneticist can help establish a definitive diagnosis and provide information on interventions.

The presenting symptoms described below, in conjunction with a family history of early renal or cardiac disease, should raise a high suspicion of Fabry disease. The diagnosis can be confirmed or ruled out in males with a blood test for α-galactosidase A (α-GAL) enzyme activity; females require genetic testing to establish a definitive diagnosis.

Common presenting symptoms

In a rheumatology setting, the most common presenting symptoms of Fabry disease are:

  • Joint pain.
  • Acute and chronic hand or foot pain, or acute agonizing episodes of radiating pain in the extremities (“Fabry crises”) lasting minutes to days. Learn more
  • Angiokeratomas: dark reddish-purple skin lesions that do not blanch with pressure and may resemble vasculitis.1 Learn more
  • Recurrent fever accompanying pain and associated with elevated erythrocyte sedimentation rate.

Angiokeratomas in Fabry disease

 angiectases are typically found between the thigh and umbilicus regions known as, "bathing suit distribution"

Characteristic lesions may be seen in the abdominal and/or buttock areas (“bathing suit distribution”), and range in size from a pinpoint to several millimeters. Used with permission from R.J. Desnick, MD, Phd.

Additional clinical findings

In addition to the common presenting symptoms discussed above, clinical findings in children and adolescents may include:

  • Fatigue.
  • Gastrointestinal problems such as abdominal pain, diarrhea, vomiting, and nausea. Learn more
  • Heat and cold intolerance. Learn more
  • Decreased ability to sweat (hypohidrosis/anhidrosis). Learn more
  • Corneal and lenticular abnormalities (seen through a slit lamp; generally do not affect vision). Learn more
  • Mild proteinuria and urinary sediment containing globotriaosylceramide.

Adolescents and adults may have:

  • Renal dysfunction leading to uremia and hypertension, and progressing to end-stage renal disease. Learn more
  • Cardiovascular dysfunction including myocardial infarction, cardiac hypertrophy, valvular abnormalities, and arrhythmias. Learn more
  • Cerebrovascular complications including early stroke, hemiplegia, hemianesthesia, and transient ischemic attacks. Learn more
  • Pulmonary complications, including airflow obstruction and dyspnea.

References:

1. Manger B, Mengel E, Schaefer R. Rheumatologic aspects of lysosomal storage diseases. Clin Rheumatol 2007;26(3):335-41.