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ODs play crucial role in identifying Fabry’s disease
Telltale corneal whorls, cataracts that appear as whitish, spot-like deposits of fine granular material near the posterior capsule and tortuosity of blood vessels on the conjunctiva and the retina can appear at a young age in patients with Fabry’s disease. With these ocular symptoms, optometrists are on the front line to diagnose these patients early and refer them for diagnostic testing and treatment.
Fabry’s disease is an inherited lysosomal storage disease in which the enzyme á-galactosidase (á-GAL), which breaks down the compound globotriaosylceramide, does not function properly or is absent, according to information provided by the School of Medicine’s Mount Sinai Department of Genetics and Genomic Sciences. As a result, globotriaosylceramide accumulates in the walls of blood vessels, eventually decreasing blood flow to the kidneys, heart, skin and nervous system. Typically, Fabry’s disease causes discomfort and pain in the hands and feet, a dark red skin rash known as angiokeratoma and characteristic changes on the cornea.
Fabry’s disease progresses slowly, and symptoms of kidney, heart or cerebrovascular involvement occur between the ages of 15 and 40, Mount Sinai said. If left untreated, Fabry’s disease leads to renal failure, cardiovascular disease or cerebrovascular disease in these patients, leading to an early death.
Corneal signs manifest early
Optometrists play a pivotal role in diagnosing Fabry’s disease because several indications of this disorder are found in the cornea at an early age.
According to Primary Care Optometry News Editorial Board member Leonid Skorin Jr., OD, DO, FAAO, FAOCO, corneal whorls (brownish or cream-colored wisps), cataracts and a patient’s blood vessels could all indicate Fabry’s.
“One of the earliest signs is corneal changes — verticillata changes — or corneal whorls that can be seen as early as childhood,” Dr. Skorin told PCON. There are also cataracts — a propeller cataract and a Fabry cataract.
“On the conjunctiva you may see secular dilation of blood vessels,” he continued. “In the retina you may see ischemic changes. Eye care practitioners who use slit lamps on a routine basis for general eye examinations would be able to see these particular changes on the cornea and make a diagnosis very early.”
Differentiating corneal whorling
Corneal whorling may be mistakenly attributed to a systemic drug the patient is taking. Albert Morier, OD, told PCON, “One of my biggest concerns is amiodarone, which is an antiarrhythmic cardiac medication. Many of us have seen corneal signs of amiodarone, and if the patient is on this medication, my fear is that the doctor will perceive it as the reason for the whorling.
“However, many patients may be on amiodarone because Fabry’s disease is affecting their heart,” Dr. Morier continued. “A patient who is 75 years old and on amiodarone is a cardiac patient; certainly a 30-year-old on amiodarone should be suspected of Fabry’s disease.”
Another concern is that eye care practitioners may disregard corneal whorls because they do not affect vision.
“Optometrists may just decide to monitor the condition,” Dr. Morier said. “We do that so often in primary care when we see something we can’t identify — if it’s not causing any problems, we tend to overlook it. You should not do that with Fabry’s disease.”
 Image: Morier A |
 Image: Desnick RJ
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Refer to a geneticist
If Fabry’s disease is suspected, optometrists should refer to someone who has expertise in diagnosing inherited metabolic diseases, Robert J. Desnick, MD, PhD, suggests.
“Optometrists can diagnose the disease and refer patients for confirmatory enzyme or DNA testing,” Dr. Desnick said in an interview. “This is important because the disease can be treated by replacing the missing enzyme activity. Studies have shown that early intervention is the most effective, before irreversible pathology has occurred.”
Because the patient may need to see many specialists — depending on how Fabry’s disease is expressed in that particular patient — Dr. Skorin recommends referring the patient to a Fabry’s disease expert at one of the larger universities who will take a team approach.
“These patients can have kidney damage, heart problems and strokes,” Dr. Skorin said. “Oftentimes you need more than one specialist, so it’s probably better when you can have a geneticist and all the other subspecialists who can check a particular part of the patient’s body.”
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| Fabry’s can cause tortuosity of blood cells on the
conjunctiva, as seen here, as well as in the retina.
Images: Desnick
RJ |
Enzyme replacement therapy
The only treatment for Fabry’s disease is an enzyme replacement therapy called Fabrazyme (agalsidase beta, Genzyme), which replaces the missing enzyme through a biweekly infusion.
“Diagnosis is made by demonstrating the deficient activity of á-GAL in plasma or leukocytes from males and the presence of the family’s specific á-GAL gene mutation in females,” Dr. Desnick said. “Enzyme replacement therapy has been shown to be effective in double-blind, randomized placebo-controlled trials. One of the trials demonstrated the effectiveness of the therapy even in older patients with advanced disease.”
According to Dr. Morier, enzyme replacement therapy seems to be helping these patients, though future technology shows great promise of developing a cure for Fabry’s.
“The signs are very good that enzyme replacement therapy can help these people, although some can have allergic reactions to the treatment,” he said. “However, with genetic gene splicing, future treatments will most likely include implanting the genome or the information to produce this enzyme.”
Genetic links
Because Fabry’s disease is an X-linked disorder, the patient’s family should also be evaluated if this disease is suspected.
“Fabry’s is inherited as an X-linked trait — males are affected and female heterozygotes can be symptomatic,” Dr. Desnick said. “Therefore, all family members should be evaluated.”
For more information:
- Leonid Skorin Jr., OD, DO, FAAO, FAOCO, is a PCON Editorial Board member who practices in Albert Lea, Minn. He may be contacted at the Albert Lea Medical Center, Mayo Health System, 404 West Fountain St., Albert Lea, MN 56007; (507) 373-8214; fax: (507) 373-2819; e-mail: skorin.leonid@mayo.edu. Dr. Skorin has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
- Albert Morier, OD, can be reached at Di Napoli Opticians, 1220 New Scotland Road, Suite 101, Slingerlands, NY 12159; (518) 439-0935; e-mail: amorier1@nycap.rr.com. Dr. Morier has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
- Robert J. Desnick, MD, PhD, is a professor and chairman of the Department of Genetics and Genomic Sciences at Mount Sinai School of Medicine in New York. He can be reached at Mount Sinai School of Medicine; (212) 659-6700; fax: (212) 360-1809; e-mail: robert.desnick@mssm.edu. Dr. Desnick has a direct financial interest in Fabrazyme and is a paid consultant for Genzyme Corp.