Laboratory Studies

Alpha-galactosidase assays are used to diagnose Fabry disease in males. Enzyme activity can be measured using patient's serum, leukocytes, tears, or cultured fibroblasts. The technique of using samples eluted from a dried blood spot collected on filter paper has allowed for high-throughput screening.^[32]However, enzyme assays only identify two thirds of heterozygote females. Thus, genetic testing is preferred for diagnosis of females. Holzl et al^[33]reported in 2010 on a fast and simple (yet sensitive) test to identify enzyme deficiencies in patients with angiokeratoma corporis diffusum Fabry disease).

Albuminuria/proteinuria are the main markers of renal dysfunction in Fabry disease. Urine sediment contains cells with birefringent lipid globules termed Maltese crosses. A few studies have shown that measuring biomarkers of glomerular (transferrin and type IV collagen) and tubular (α1-microglobulin, N-acetyl-β-glucosaminidase, and alanine aminopeptidase) dysfunction may be more accurate than albuminuria in identifying Fabry nephropathy.^[34]

Papaxanthos-Roche et al^[35]noted that azoospermia can be a feature of Fabry disease.

Novel Gb(3) isoforms can be found in patients with Fabry disease.^[36]

Pereira et al^[37]found the lysosome-associated membrane proteins (LAMP) 1 and 2 are normal in normal controls and normalize with treatment with alpha-galactosidase. This helps to measure the effective of enzyme replacement therapy.

Using a mouse model, Shu et al^[38]found that 3-nitrotyrosine can function as a marker for Fabry disease–related vasculopathy.

Imaging Studies

A variety of imaging studies can be used to evaluate Fabry disease. These include cardiac, body, and brain imaging tests.

Neurological

In a group of young Fabry disease patients with normal MRI findings, a significant increment of greater than 12% in apparent diffusion coefficient values in the corona radiata occurred compared with age-matched controls. The difference might demonstrate increased interstitial water in tissue after the Starling equilibrium under raised cerebral blood flow. This increase water content has been previously defined as a manifestation of Fabry disease. Thus, increased apparent diffusion coefficient values might occur before conventional MRI changes in persons with Fabry disease. Increased apparent diffusion coefficient values seem to be a sensitive marker of disease progression and the healing effect of enzymatic replacement therapy.^[39]

Cardiac

Echocardiography can disclose left ventricular hypertrophy and systolic anterior motion of the mitral leaflets. Cardiac catheterization can show marked gradient loss in the left ventricular peak systolic outflow gradient, which indicates the presence of left ventricular outflow obstruction. Cardiac MRI might play a role in evaluating the effectiveness of enzyme therapy for Fabry disease.^[40]

Other Tests

Slit-lamp examination of the eyes of patient with Fabry disease can reveal a whorl-like keratopathy.^[41]Thus, ophthalmic examination can be useful in defining Fabry disease.

A variety of neurological tests can be done to detect small-fiber neuropathy in Fabry disease and other small-fiber diseases that involve neuropathy.^[42]

Procedures

Slit-lamp ophthalmologic examination demonstrates characteristic corneal opacity. Also, look for the unique spokelike cataracts in the posterior capsule.

Tissue biopsy can aid in diagnosis.

Histologic Findings

Histology shows numerous, dilated, thin-walled, endothelial-lined, blood-engorged capillaries in the papillary dermis, with an overlying hyperkeratotic epidermis. Careful inspection may reveal cytoplasmic vacuoles containing lipid in the endothelial cells, fibroblasts, and pericytes. However, in most patients, histologic findings essentially are identical to those of other angiokeratomas.

Endomyocardial biopsy findings of the heart can demonstrate sarcoplasmic vacuolization of cardiac muscle cells under light microscopy and lamellated zebra bodies in the cytoplasm under electron microscopy.

Electromicroscopy investigation can show stromal cells in hemizygous tissue and endothelial and smooth muscle cells in heterozygous tissue; cells contain membrane-bound inclusions with a lamellar structure (ie, inclusion bodies with a zebralike appearance).

Treatment & Management

U.S. National Library of Medicine, part of the National Institutes of Health,. GLA. Genetics Home Reference. Available at http://ghr.nlm.nih.gov/gene=gla. Accessed: June 21, 2009.
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Media Gallery

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

of 3

Author

Fnu Nutan, MD, FACP Assistant Professor, Department of Dermatology, Virginia Commonwealth University School of Medicine

Fnu Nutan, MD, FACP is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, Indian Association of Dermatologists, Venereologists and Leprologists, Society of General Internal Medicine, Society of Hospital Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Julie Zixuan Yi MD Candidate, Eastern Virginia Medical School

Julie Zixuan Yi is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Rosalie Elenitsas, MD Herman Beerman Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System

Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society of Dermatopathology, Pennsylvania Academy of Dermatology

Disclosure: Received royalty from Lippincott Williams Wilkins for textbook editor.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Additional Contributors

Timothy McCalmont, MD Director, UCSF Dermatopathology Service, Professor of Clinical Pathology and Dermatology, Departments of Pathology and Dermatology, University of California at San Francisco; Editor-in-Chief, Journal of Cutaneous Pathology

Timothy McCalmont, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society of Dermatopathology, California Medical Association, College of American Pathologists, United States and Canadian Academy of Pathology

Disclosure: Received consulting fee from Apsara for independent contractor.

Noah S Scheinfeld, JD, MD, FAAD † Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Anusuya Mokashi, MD, MS Resident Physician, Department of Radiology, Staten Island University Hospital

Disclosure: Nothing to disclose.

Acknowledgements

Arnold R Oppenheim, MD Assistant Professor, Department of Internal Medicine, Division of Dermatology, Eastern Virginia School of Medicine

Arnold R Oppenheim, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Clinical Pathology

Disclosure: Nothing to disclose.