Angiokeratoma Corporis Diffusum (Fabry Disease) Workup

Updated: Nov 21, 2019
  • Author: Fnu Nutan, MD, FACP; Chief Editor: William D James, MD  more...
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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.


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]


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]



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).