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Genetics of Fabry Disease Workup

  • Author: Robert J Desnick, MD, PhD; Chief Editor: Maria Descartes, MD  more...
Updated: Feb 24, 2016

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[2] and other experts in the field.[3] 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:

CBC count, 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.[4]

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.

Contributor Information and Disclosures

Robert J Desnick, MD, PhD Dean for Genetics and Genomics, Professor and Chairman, Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine

Robert J Desnick, MD, PhD is a member of the following medical societies: American Society for Biochemistry and Molecular Biology, Eastern Society for Pediatric Research, American College of Medical Genetics and Genomics, American Pediatric Society, American Society for Clinical Investigation, American Society for Microbiology, American Society of Human Genetics, Central Society for Clinical and Translational Research, New York Academy of Sciences, Sigma Xi, Society for Experimental Biology and Medicine, Society for Pediatric Research

Disclosure: Received consulting fee from Amicus Therapeutics for consulting; Received consulting fee from Genzyme for consulting; Received grant/research funds from Genzyme for consulting; Received royalty from Genzyme for none; Received scientific advisory board from Genzyme for none; Received consulting fee from Synageva BioPharma for none; Received stock options from Synageva BioPharma for none; Received royalty from Shire HGT for none.


Kenneth H Astrin, PhD Associate Professor of Human Genetics, Department of Human Genetics, Mount Sinai School of Medicine

Kenneth H Astrin, PhD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Nothing to disclose.

Maryam Banikazemi, MD Assistant Professor of Clinical Pediatrics, New York Medical College

Maryam Banikazemi, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Robert D Steiner, MD Chief Medical Officer, Acer Therapeutics; Clinical Professor, University of Wisconsin School of Medicine and Public Health

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics and Genomics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Acer Therapeutics; Retrophin; Raptor Pharma; Veritas Genetics; Censa Pharma<br/>Received income in an amount equal to or greater than $250 from: Acer Therapeutics; Retrophin; Raptor Pharma; Censa Pharma.

David Flannery, MD, FAAP, FACMG Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics

Disclosure: Nothing to disclose.

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Angiokeratoma is the small punctate reddish-to-bluish angiectases on the umbilicus.
Angiokeratomas are commonly observed as dense cluster of lesions on the flank and private areas.
Corneal verticillata, commonly seen in patients with Fabry disease, detectable by slit lamp examination.
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