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Patient exhibits corneal verticillata for more than 20 years
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This 38-year-old white female first presented 2 years earlier for an assessment after having poked her left eye with her own finger. During that examination the patient was noted to have corneal verticillata. Other eye doctors had told her she had these corneal findings since the age of 12.
The patient had also undergone successful LASIK for myopia correction at the age of 32, and corneal verticillata were noted at her consult for refractive surgery. Corneal photography was performed, and the patient was questioned about medication use as a possible cause. No further work-up ensued.
After her assessment of the eye injury and reaffirmed diagnosis of corneal verticillata by her optometrist at age 36, the patient was referred for genetic counseling. An initial visit with a genetic pediatrician found an otherwise healthy individual other than a long-standing history of irritable bowel syndrome and anxiety. The patient was recommended for enzymatic and DNA testing. She has no children at this time.
Corneal verticillata were seen in this patient since the age of 12.
Image: Morier A
After the patient was lost to follow-up for close to a year, she was finally diagnosed with Fabry’s disease after she was found to have one copy of the R220X mutation.
Incidence, symptoms
Fabry’s disease is a progressive, debilitating and often life-threatening X-linked inherited disorder. The incidence is traditionally estimated to be 1 in 40,000 live births (Mehta et al.). It is an inborn error of metabolism resulting in deficient enzyme levels of the lysosomal enzyme alpha-galactosidase A (a-GAL).
A-GAL deficiency prevents the effective metabolism of the glycoprotein globotriaosylceramide (Gb3). Consequently, Gb3 accumulates in lysosomes of vascular endothelial cells resulting in an intrinsic inflammatory cascade in virtually every tissue in the body.
Initially, symptoms include angiokeratomas (telangiectatic cutaneous lesions), acroparesthesia (severe pain in hands and feet), hypohidrosis (inability to sweat), gastrointestinal dysmotility and various ocular manifestations. As the disease progresses, vascular complications of major organ systems ensue, leading to kidney failure, cardiomyopathy and stroke. While previously thought to exclusively involve males, it is now clear that women can also be affected depending on the variable level of X-inactivation during embryonic development. Therefore, both males and females can display a unique clinical presentation of signs and symptoms across a spectrum of disease manifestations.
Ocular manifestations
Ocular manifestations of Fabry’s disease have been published by several investigators. The most commonly reported ocular finding is corneal verticillata, a bilateral, whorl-like pattern of cream-colored lines usually found in the inferior cornea, radiating outward. These deposits can range from faint to pronounced and are located at the level of Bowman’s membrane. They can be seen as early as 6 months of age and fully apparent by age 10.
Corneal whorling from both Fabry’s disease and the use of the cardiac anti-arrhythmic, amiodarone, occur at the same level within the cornea. It is important to note that a patient with corneal whorling who is taking amiodarone may have hypertrophic cardiomyopathy as a result of Fabry’s disease. It is crucial that one does not assume the cause is the amiodarone, especially if the patient is young.
Conjunctival and retinal blood vessels may exhibit tortuosity and aneurysmal dilations. The pathophysiology is primarily caused by Gb3 accumulation within the vessel walls, resulting in endothelial cell dysfunction, abnormal blood flow and hypercoagulability. While blood vessel tortuosity is often seen among all patients, aneurysmal dilations are not and are a sign that the disease is at a more advanced level.
Two types of lenticular changes are associated with Fabry’s disease. One is a granular anterior capsular or subcapsular deposit radiating out from the periphery in a pattern that has been described as a ‘‘propeller cataract.’’ The other is a whitish, faint, linear cataract at or near the posterior lens capsule.
This second type of cataract was first described by Spaeth and Frost in 1965 and is termed a Fabry cataract, as it seems to be unique to this condition. This is particularly difficult to see, as it is translucent and best seen by retro-illumination.
Current status of patient
This patient continues to be in fairly good health with no evidence of clinical symptoms associated with Fabry’s disease. She reports improvement with her anxiety and irritable bowel syndrome. She is followed on an annual basis by a geneticist, optometrist, neurologist, cardiologist and dermatologist.
Treatment with Fabrazyme (agalsidase beta, Genzyme) enzyme replacement therapy has not been initiated at this time. Her family will be monitored for evidence of the condition.
The ocular manifestations of Fabry’s disease are signs that a fatal insidious disease is lurking within the patient’s genetic code, slowly damaging the kidney, heart and brain. The nonfatal effects of the disease – acroparesthesia (pain in hands and feet), angiokeratoma (vascular skin lesions), hypohidrosis or anhidrosis (poor or nonexistent sweating) and gastrointestinal maladies (i.e., spontaneous diarrhea) – make for poor quality of life.
Females carriers are affected as much as males (although this takes a longer time), which is contrary to what we were taught in our basic genetic courses where female carriers have the affected gene but do not express it. With careful observation, eye care professionals can hasten the diagnosis and have a major impact on the lives of the patient, their siblings and their progeny.
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