Transcript Fabry`s
My Name is Fabry Laura S Gilmore, MD Department of Ophthalmology TTUHSC September 10, 2004 Discussants: Kelly Mitchell, MD Kenn Freedman, MD 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. 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 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???