Genetics of Fabry Disease Workup

Updated: Aug 23, 2018
  • Author: Robert J Desnick, MD, PhD; Chief Editor: Maria Descartes, MD  more...
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Laboratory Studies

The following studies are indicated in Fabry disease:

α-Gal A

α-Gal A activity may be measured in plasma, serum, and leukocytes. Tissue biopsies and cultured skin fibroblasts may also be used to measure a-Gal A activity.

In males with the classic or variant phenotype, the disease is readily diagnosed based on low α-Gal A activity.

Female carriers may have α-Gal A activity that ranges from zero to within the reference range. Thus, enzyme assays are rarely helpful in determining female carrier status.

DNA analysis

DNA isolated from blood or biopsy specimens can be used for analysis of the α-Gal A gene sequence to identify the disease-causing mutation. DNA testing is the preferred method for identifying and confirming the carrier status of females in whom enzyme activity is within or near the reference range.

Laboratory tests after diagnosis

After the diagnosis has been confirmed using enzyme assays, DNA testing, or both, carefully assess the patient. A recommended minimum assessment schedule has been developed by the Fabry Board of Advisors [5] and other experts in the field. [6] The recommended assessment frequency depends on patient age and previous findings. Females and males should undergo the same degree of assessment and monitoring. The following recommended laboratory assessments should be obtained at baseline and at appropriate intervals:

Complete blood count (CBC), serum electrolyte level measurement, and lipid profile

Obtain at baseline and appropriate intervals.

Renal evaluation

Serum BUN and creatinine levels and 24-hour urine or spot urine measurement for total protein/creatinine, albumin/creatinine, sodium, creatinine, and urinary GL-3 (optional) levels. [2]

Renal biopsy (This may be warranted in atypical cases to exclude any other causes of renal disease.)


Imaging Studies

CNS evaluation

MRI is used to document evidence of brain ischemic disease.

Magnetic resonance angiography (MRA) may be indicated to assess cerebral vasculopathy.

Peripheral nerves should be periodically assessed using a detailed neurological examination.


Other Tests

Cardiac evaluation

Ventricular hypertrophy and septal thickening can be demonstrated using echocardiography. If left ventricular hypertrophy (LVH) is present, a cardiac MRI with contrast can be performed to evaluate the presence of scarring.

Abnormal ECG findings include sinus bradycardia, nonspecific ST-segment changes, T-wave inversion, and shortened PR interval. Evidence of LVH and previous ischemic injury may also be present.

Holter monitoring in selected patients may provide important information.

Psychosocial evaluation

All health-care professionals who treat patients with Fabry disease should be sensitive to the psychosocial burden of a chronic, rare, and progressive disease. In these families, denial, guilt, and anger frequently play a significant role in intrafamilial dynamics. Pay special attention to the history and signs of anxiety disorders, clinical depression, suicidal ideation or attempts, and substance abuse.

Pulmonary evaluation

Perform induced sputum analysis, lung biopsy, or both if severe pulmonary involvement is present (to exclude an intercurrent disease process).

Visual evaluation

Perform slit-lamp microscopy to identify the typical Fabry disease–specific changes in the cornea, lens, retina, and conjunctiva.