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Woman With Sudden Loss of Vision—Diagnosis

Woman With Sudden Loss of Vision—Diagnosis Diagnosis Homocystinuria What to Do Next D. Concurrent laboratory studies checking rapid plasmin reagin, fluorescent treponemal antibody absorption, and serum homocysteine levels On the day of presentation, laboratory studies were drawn for rapid plasmin reagin, fluorescent treponemal antibody absorption, and serum homocysteine. Pars plana lensectomy/vitrectomy was performed on the patient's right eye without complication. The patient experienced a normal postoperative course, with final right eye best-corrected visual acuity of 20/25. The laboratory examination results were negative for rapid plasmin reagin and fluorescent treponemal antibody absorption. The serum homocysteine level was elevated at 47.4 μmol/L (reference range, 5.4-11.9 μmol/L). A clinical diagnosis of homocystinuria was made, and the patient began treatment with oral pyridoxine phosphate, 200 mg/d. She was referred to her primary care physician for follow-up of her homocysteine level. Comment The differential diagnosis for bilateral lens subluxation in the absence of reported trauma includes untreated syphilis or hereditary diseases, such as Marfan syndrome, homocystinuria, Weill Marchesani syndrome, and other rare disorders, such as hyperlysinemia and sulfite oxidase deficiency.1 Owing to the unique systemic manifestations and complications of each of these disorders, it is imperative that the ophthalmologist not only treat the ocular disorder but take a careful family history followed by referral for a full physical examination including evaluation for murmurs, hyperextensibility, and abnormal digits. In the absence of any suspicious findings (as in our patient), initial evaluation should begin with laboratory studies testing for elevated homocysteine levels and syphilis. If the results of these tests prove negative, then further testing should include electrocardiogram, echocardiogram, and referral to a cardiologist to ensure there are no abnormalities suggestive of previously undiagnosed Marfan syndrome. A geneticist may also be consulted for assessment of more specific mutations. In our patient, initial testing revealed an elevated serum homocysteine level. Homocystinuria is the second most common treatable amino acid metabolism disorder, with an estimated worldwide prevalence of 1:344 000, although there is a notably high incidence in Ireland (1:65 000).2 It is an autosomal recessive condition resulting in a deficiency of the enzyme cystathionine β-synthase and a subsequent increase in plasma homocysteine and decrease in cysteine. The disease may affect the skeletal, vascular, and central nervous systems, and ectopia lentis may occur in up to 90% of untreated patients.2,3 Zonular fibers consist primarily of cysteine-rich glycoproteins with abundant collagen cross-linking, which are thought to interact with sulfhydryl groups on the excess homocysteine. The reduced cysteine availability and impaired collagen cross-linking leads to reduced zonule integrity and lens subluxation, typically inferonasally, which is in contrast to superior dislocation typical of Marfan syndrome.4 In untreated homocystinuria, lens subluxation is often the first ocular presentation, preceding other sight-threatening complications such as secondary glaucoma and retinal detachment.3 Vascular disease complications cause the most morbidity and mortality for patients with homocystinuria, with 50% of untreated patients having a vascular event before the age of 30 years (30% before age 20 years).2 High levels of homocysteine have been implicated, with an increased risk for stroke, coronary artery disease, and arterial and venous thromboembolism.5 This thromboembolic risk is dramatically increased in patients receiving general anesthesia, requiring more extensive intravenous hydration. Many mechanisms have been proposed for the thromboembolic propensity, including increased platelet adhesiveness due to the elevated homocysteine levels.6 The risk for life-threatening vascular disease makes prompt identification and treatment of homocystinuria crucial, with only mildly elevated levels of homocysteine now considered a risk factor for premature atherosclerosis.7 Treatment consists of oral pyridoxine, 200 mg daily, in association with a low methionine diet.2 Betaine, folic acid, and Vitamin B12 may be used as adjuncts, and patients should avoid oral contraceptive use. Chronic treatment with normalization of serum homocysteine levels significantly reduces the risk for thromboembolic events.2 The risk of ectopia lentis may only be reduced if treatment is started within 6 weeks of birth.8 Keeping in mind the vascular and ocular problems associated with homocystinuria, it is imperative to consider homocystinuria in patients with ectopia lentis and test appropriately in initial evaluation. Return to Quiz Case Back to top Article Information Correspondence: Jayanth Sridhar, MD, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, 900 NW 17th Street, Miami, FL 33136 (jsridhar@med.miami.edu). Submitted for Publication: November 12, 2012; final revision received December 30, 2012; accepted January 29, 2013. Conflict of Interest Disclosures: None reported. References 1. Anteby I, Isaac M, BenEzra D. Hereditary subluxated lenses: visual performances and long-term follow-up after surgery. Ophthalmology. 2003;110(7):1344-134812867389PubMedGoogle ScholarCrossref 2. Yap S. Classical homocystinuria: vascular risk and its prevention. J Inherit Metab Dis. 2003;26(2-3):259-26512889665PubMedGoogle ScholarCrossref 3. Harrison DA, Mullaney PB, Mesfer SA, Awad AH, Dhindsa H. Management of ophthalmic complications of homocystinuria. Ophthalmology. 1998;105(10):1886-18909787359PubMedGoogle ScholarCrossref 4. Grieco AJ. Homocystinuria: pathogenetic mechanisms. Am J Med Sci. 1977;273(2):120-132324277PubMedGoogle ScholarCrossref 5. Prasad K. Homocysteine, a risk factor for cardiovascular disease. Int J Angiol. 1999;8(1):76-869826415PubMedGoogle ScholarCrossref 6. Cline JW, Goyer RA, Lipton J, Mason RG. Adult homocystinuria with ectopia lentis. South Med J. 1971;64(5):613-6174396748PubMedGoogle ScholarCrossref 7. Bakker RC, Brandjes DP. Hyperhomocysteinaemia and associated disease. Pharm World Sci. 1997;19(3):126-1329259028PubMedGoogle ScholarCrossref 8. Taylor RH, Burke J, O’Keefe M, Beighi B, Naughton E. Ophthalmic abnormalities in homocystinuria: the value of screening. Eye (Lond). 1998;12(pt, 3a):427-4309775245PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Ophthalmology American Medical Association

Woman With Sudden Loss of Vision—Diagnosis

JAMA Ophthalmology , Volume 131 (4) – Apr 1, 2013

Woman With Sudden Loss of Vision—Diagnosis

Abstract

Diagnosis Homocystinuria What to Do Next D. Concurrent laboratory studies checking rapid plasmin reagin, fluorescent treponemal antibody absorption, and serum homocysteine levels On the day of presentation, laboratory studies were drawn for rapid plasmin reagin, fluorescent treponemal antibody absorption, and serum homocysteine. Pars plana lensectomy/vitrectomy was performed on the patient's right eye without complication. The patient experienced a normal postoperative course, with final...
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Publisher
American Medical Association
Copyright
Copyright © 2013 American Medical Association. All Rights Reserved.
ISSN
2168-6165
eISSN
2168-6173
DOI
10.1001/jamaophthalmol.2013.304b
Publisher site
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Abstract

Diagnosis Homocystinuria What to Do Next D. Concurrent laboratory studies checking rapid plasmin reagin, fluorescent treponemal antibody absorption, and serum homocysteine levels On the day of presentation, laboratory studies were drawn for rapid plasmin reagin, fluorescent treponemal antibody absorption, and serum homocysteine. Pars plana lensectomy/vitrectomy was performed on the patient's right eye without complication. The patient experienced a normal postoperative course, with final right eye best-corrected visual acuity of 20/25. The laboratory examination results were negative for rapid plasmin reagin and fluorescent treponemal antibody absorption. The serum homocysteine level was elevated at 47.4 μmol/L (reference range, 5.4-11.9 μmol/L). A clinical diagnosis of homocystinuria was made, and the patient began treatment with oral pyridoxine phosphate, 200 mg/d. She was referred to her primary care physician for follow-up of her homocysteine level. Comment The differential diagnosis for bilateral lens subluxation in the absence of reported trauma includes untreated syphilis or hereditary diseases, such as Marfan syndrome, homocystinuria, Weill Marchesani syndrome, and other rare disorders, such as hyperlysinemia and sulfite oxidase deficiency.1 Owing to the unique systemic manifestations and complications of each of these disorders, it is imperative that the ophthalmologist not only treat the ocular disorder but take a careful family history followed by referral for a full physical examination including evaluation for murmurs, hyperextensibility, and abnormal digits. In the absence of any suspicious findings (as in our patient), initial evaluation should begin with laboratory studies testing for elevated homocysteine levels and syphilis. If the results of these tests prove negative, then further testing should include electrocardiogram, echocardiogram, and referral to a cardiologist to ensure there are no abnormalities suggestive of previously undiagnosed Marfan syndrome. A geneticist may also be consulted for assessment of more specific mutations. In our patient, initial testing revealed an elevated serum homocysteine level. Homocystinuria is the second most common treatable amino acid metabolism disorder, with an estimated worldwide prevalence of 1:344 000, although there is a notably high incidence in Ireland (1:65 000).2 It is an autosomal recessive condition resulting in a deficiency of the enzyme cystathionine β-synthase and a subsequent increase in plasma homocysteine and decrease in cysteine. The disease may affect the skeletal, vascular, and central nervous systems, and ectopia lentis may occur in up to 90% of untreated patients.2,3 Zonular fibers consist primarily of cysteine-rich glycoproteins with abundant collagen cross-linking, which are thought to interact with sulfhydryl groups on the excess homocysteine. The reduced cysteine availability and impaired collagen cross-linking leads to reduced zonule integrity and lens subluxation, typically inferonasally, which is in contrast to superior dislocation typical of Marfan syndrome.4 In untreated homocystinuria, lens subluxation is often the first ocular presentation, preceding other sight-threatening complications such as secondary glaucoma and retinal detachment.3 Vascular disease complications cause the most morbidity and mortality for patients with homocystinuria, with 50% of untreated patients having a vascular event before the age of 30 years (30% before age 20 years).2 High levels of homocysteine have been implicated, with an increased risk for stroke, coronary artery disease, and arterial and venous thromboembolism.5 This thromboembolic risk is dramatically increased in patients receiving general anesthesia, requiring more extensive intravenous hydration. Many mechanisms have been proposed for the thromboembolic propensity, including increased platelet adhesiveness due to the elevated homocysteine levels.6 The risk for life-threatening vascular disease makes prompt identification and treatment of homocystinuria crucial, with only mildly elevated levels of homocysteine now considered a risk factor for premature atherosclerosis.7 Treatment consists of oral pyridoxine, 200 mg daily, in association with a low methionine diet.2 Betaine, folic acid, and Vitamin B12 may be used as adjuncts, and patients should avoid oral contraceptive use. Chronic treatment with normalization of serum homocysteine levels significantly reduces the risk for thromboembolic events.2 The risk of ectopia lentis may only be reduced if treatment is started within 6 weeks of birth.8 Keeping in mind the vascular and ocular problems associated with homocystinuria, it is imperative to consider homocystinuria in patients with ectopia lentis and test appropriately in initial evaluation. Return to Quiz Case Back to top Article Information Correspondence: Jayanth Sridhar, MD, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, 900 NW 17th Street, Miami, FL 33136 (jsridhar@med.miami.edu). Submitted for Publication: November 12, 2012; final revision received December 30, 2012; accepted January 29, 2013. Conflict of Interest Disclosures: None reported. References 1. Anteby I, Isaac M, BenEzra D. Hereditary subluxated lenses: visual performances and long-term follow-up after surgery. Ophthalmology. 2003;110(7):1344-134812867389PubMedGoogle ScholarCrossref 2. Yap S. Classical homocystinuria: vascular risk and its prevention. J Inherit Metab Dis. 2003;26(2-3):259-26512889665PubMedGoogle ScholarCrossref 3. Harrison DA, Mullaney PB, Mesfer SA, Awad AH, Dhindsa H. Management of ophthalmic complications of homocystinuria. Ophthalmology. 1998;105(10):1886-18909787359PubMedGoogle ScholarCrossref 4. Grieco AJ. Homocystinuria: pathogenetic mechanisms. Am J Med Sci. 1977;273(2):120-132324277PubMedGoogle ScholarCrossref 5. Prasad K. Homocysteine, a risk factor for cardiovascular disease. Int J Angiol. 1999;8(1):76-869826415PubMedGoogle ScholarCrossref 6. Cline JW, Goyer RA, Lipton J, Mason RG. Adult homocystinuria with ectopia lentis. South Med J. 1971;64(5):613-6174396748PubMedGoogle ScholarCrossref 7. Bakker RC, Brandjes DP. Hyperhomocysteinaemia and associated disease. Pharm World Sci. 1997;19(3):126-1329259028PubMedGoogle ScholarCrossref 8. Taylor RH, Burke J, O’Keefe M, Beighi B, Naughton E. Ophthalmic abnormalities in homocystinuria: the value of screening. Eye (Lond). 1998;12(pt, 3a):427-4309775245PubMedGoogle ScholarCrossref

Journal

JAMA OphthalmologyAmerican Medical Association

Published: Apr 1, 2013

Keywords: sudden visual loss

References