Fabry’s disease

• 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 --> globotriaosylceramide accumulates in the walls of blood vessels --> eventually decreasing blood flow to the kidneys, heart, skin and nervous system
• progresses slowly
• symptoms of kidney, heart or cerebrovascular involvement occur between the ages of 15 and 40
• if left untreated, Fabry’s disease leads to renal failure, cardiovascular disease or cerebrovascular disease in these patients, leading to an early death.

Symptoms

• discomfort and pain in the hands and feet
• dark red skin rash known as angiokeratoma

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
• corneal whorls (brownish or cream-colored wisps)
• cataracts -- a propeller cataract and a Fabry cataract (whitish, spot-like deposits of fine granular material near the posterior capsule)
• secular dilation of blood vessels on the conjunctiva
• ischemic changes in the retina (vessel dilation)
• many patients may be on amiodarone because Fabry’s disease is affecting their heart. 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

Refer to a geneticist + specialists

• refer patients for confirmatory enzyme or DNA testing,” Dr. Desnick said in an interview
• 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 refer the patient to a Fabry’s disease expert at one of the larger universities who will take a team approach.

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
• Enzyme replacement therapy has been shown to be effective in double-blind, randomized placebo-controlled trials, even in older patients with advanced disease

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