My Name is

Fabry

Laura S Gilmore, MD Department of Ophthalmology TTUHSC September 10, 2004 Discussants: Kelly Mitchell, MD Kenn

Freedman, MD

Case PresentationCC: Loss of vision, chest painHPI: 55yo HF with sudden onset of visual loss OD

approximately two hours prior to presentation in EDP.O.H.: CRAO OS 1 week ago P.M.H.: HTN. ESRD. CAD s/p CABG. CVA. NQWMI.Meds: Procardia. Lipitor. Clonidine. ASA. TylenolS.H.: Denies tobacco/alcohol.F.H.: CA, CAD. Denies family history of ocular disease. R.O.S.: +chest pain, s/p NQWMI 1 week ago. Persistent

visual loss OS, new visual loss OD. No HA, scalp tenderness, jaw claudication, anorexia, dizziness, tinnitus. No recent change in weight.

Physical Exam/Initial WorkupVS: BP 180/104 (228/110 1 week prior) EKG: new NQWMI, old NQWMIVA sc: HM at 6” OD, LP OSPupils: 6 NR OU CT/MRI: normalIOP: 16, 13 ESR: 12E.O.M.: Full O.U. S.L.E.: mild subepithelial infiltrates OUD.F.E.: pale fundi OU with macular cilioretinal

sparing OD, cherry-red spot OU. Tortuous retinal vessels OU. 1+ ONH pallor. 2+ NFL edema

Additional History (provided by family)

Patient’s brother and nephew with Fabry’s, with multiple CVA’s and MI’s in late 20’s and early 30’s; died in early 30’s

Patient’s 24 yo son with Fabry’s, first CVA at age 17, on ERT since.

Patient tested-leukocyte alpha-galactosidase A level low

CRAO Demographics:

• 50-80yo; 1/10,000 incidence• Sudden, painless, unilateral vision loss;1-2%

bilateral

Findings:• Diffusely pale retina• Cherry-red macula

Treatment/Outcome:• Neovascularization uncommon (16%)• Treatment targeted at restoring blood flow• Visual loss generally severe, persistent despite

efforts

Outcome Vision at presentation often CF to LP

and remains so in spite of treatment If improved, often only one-quarter

line of Snellen acuity improvement; in some reports, 35% get VA of 20/200 and 20% get 20/40

GCA is high on differential, and can lead to severe bilateral vision loss if undetected

Overall significantly reduced survival rate, mostly due to cardiac disease

Things to Keep in Mind with CRAO

Between 2 and 10% from GCA 75% have carotid atherosclerosis or systemic HTN Cardiac emboli Collagen vascular disease Migrainous vasospasm Compressive lesions-optic nerve drusen, papillitis,

papilledema, AION, retrobulbar injection, CRVO, neoplasm

Blood dyscrasias-Sickle Cell Disease Antiphospholipid syndrome Idiopathic Lipid storage disease?-Fabry’s-one other case report

Workup ESR, CRP and homocysteine levels normal BP evaluation EKG-NQWMI Lipid and cholesterol levels-normal Coagulation studies-normal Cardiology eval-Carotid ultrasound negative for

stenosis bilaterally; ECHO showed mild LVH, no valvular vegetations or abnormalities, no septal defect, no thrombus

CT and MRI-no acute findings

Fabry’s

First described in 1898 X-linked recessive lipid storage disorder Defect in alpha-Galactosidase A, which

breaks down globotriasolyceramide, or Gb3 Gb3 Accumulates in vascular endothelium

of kidneys, heart, nerves, blood vessels

More Overview

Widely variable presentation Diagnosis often delayed or overlooked-average age

of symptom onset is 10.5 years, average age of diagnosis is 28.5 years

Rare-1/40,000 males All ethnicities Some females express varying clinical features,

despite being X-linked Heterozygous women are usually asymptomatic or

are only minimally affected

Signs and Symptoms Clouding of cornea-corneal whorls or opacification Burning sensations in hands and feet, worse with

exercise and hot weather Heat or cold intolerance Impaired sweating Small raised, reddish-purple blemishes on the skin-

angiokeratoma Impairment of arterial circulation-risk for MI and

CVA Renal failure-dialysis or transplant GI difficulties Recurrent fever

Ocular Manifestations of Fabry’s

Characteristic cream-colored, whorl-like corneal opacity

Tortuosity of conjunctival and retinal vessels Cream-colored anterior lens capsular deposits Posterior capsular opacity with a radial pattern. The whorl-like corneal opacity that is sometimes

called “cornea verticillata” is seen in almost all of the heterozygotes, more prominently than in the hemizygotes.

Diagnostic Testing

Histopathologic examination of skin biopsy Low alpha-galactosidase activity in

leukocytes Genetic examination

Course

Most survive into adulthood At risk for heart attack, stroke, kidney

damage Enzyme replacement therapy has been

approved Mainly treat symptoms

 

Treatment Monitor kidney function-low protein diet,

dialysis, or transplant Heart problems including angina, enlargement,

valve abnormalities-medical management, angioplasty, bypass, pacemaker

Cerebrovascular-anticoagulation Tegretol or dilantin for pain in extremities,

avoid certain strenuous activities, increase liquid intake, frequent breaks, be prepared for changing weather

Metaclopramide, low fat diet for GI symptoms of pain, nausea, diarrhea

Removal of skin rash with laser

Conclusion CRAO and Fabry's are rare Fabry’s as the cause of CRAO is rarer still (only one

reported case) A bilateral case of CRAO requires a thorough workup

because those hoofbeats might belong to a zebra

Any Questions???