My Name is Fabry

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My Name is Fabry

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

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Case Presentation

• CC Loss of vision, chest pain
• HPI 55yo HF with sudden onset of visual loss OD
  approximately two hours prior to presentation in
  ED
• P.O.H. CRAO OS 1 week ago
• P.M.H. HTN. ESRD. CAD s/p CABG. CVA. NQWMI.
• Meds Procardia. Lipitor. Clonidine. ASA. Tylenol
• S.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.

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Physical Exam/Initial Workup

• VS BP 180/104 (228/110 1 week prior)
• EKG new NQWMI, old NQWMI
• VA sc HM at 6 OD, LP OS
• Pupils 6 NR OU CT/MRI normal
• IOP 16, 13 ESR 12
• E.O.M. Full O.U.
• S.L.E. mild subepithelial infiltrates OU
• D.F.E. pale fundi OU with macular cilioretinal
  sparing OD, cherry-red spot OU. Tortuous retinal
  vessels OU. 1 ONH pallor. 2 NFL edema

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Additional History (provided by family)

• Patients brother and nephew with Fabrys, with
  multiple CVAs and MIs in late 20s and early
  30s died in early 30s
• Patients 24 yo son with Fabrys, first CVA at
  age 17, on ERT since.
• Patient tested-leukocyte alpha-galactosidase A
  level low

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CRAO

• Demographics
• 50-80yo 1/10,000 incidence
• Sudden, painless, unilateral vision loss1-2
  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

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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

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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?-Fabrys-one other case
  report

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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

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Fabrys

• 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

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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

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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

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Ocular Manifestations of Fabrys

• 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.

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Diagnostic Testing

• Histopathologic examination of skin biopsy
• Low alpha-galactosidase activity in leukocytes
• Genetic examination

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Course

• Most survive into adulthood
• At risk for heart attack, stroke, kidney damage
• Enzyme replacement therapy has been approved
• Mainly treat symptoms

 
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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

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Conclusion

• CRAO and Fabry's are rare
• Fabrys 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???