Case Report FEVR-Like Presentation of Homocystinuria Lorena A. Montalvo, Vincent D. Venincasa, Hassan A. Aziz, Ditte Hess, and Audina M. Berrocal Bascom Palmer Eye Institute, University of Miami, 900 NW 17th Street, Miami, FL 33136, USA Correspondence should be addressed to Audina M. Berrocal; [email protected] Received 16 September 2014; Accepted 27 October 2014; Published 13 November 2014 Academic Editor: J. Fernando Arevalo Copyright © 2014 Lorena A. Montalvo et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A male infant with a diagnosis of homocystinuria presented with avascularity of the peripheral retina with a ridge on ophthalmic exam, consistent with a FEVR-like manifestation homocystinuria. Upon follow-up and treatment for homocystinuria, the retinal vascularity improved without the need for prophylactic treatment to the peripheral avascular retina. 1. Introduction Homocystinuria is a rare disorder caused by a defect in methionine metabolism due to inadequate activity of the enzyme cystathionine beta synthase (CBS) [1]. is results in hyperhomocysteinemia, which is associated with cardiovas- cular disease (i.e., increased risk of abnormal blood clotting), mild cognitive impairment, and dementia. Ocular manifes- tations of homocystinuria include ectopia lentis, glaucoma, macular degeneration, maculopathy, retinal degeneration, and retinal vascular diseases, such as central retinal vein occlusion, branch retinal vein occlusion, and central retinal artery occlusion [2]. Familial exudative vitreoretinopathy (FEVR) is a progres- sive eye disease that affects the vascularization of the periph- eral retina [3]. e characteristic manifestations of FEVR include avascularity of the peripheral retina, temporal drag- ging of the vascular arcades, and heterotopia of the macula. Progression of the disease is indicated with subretinal exu- dates and tractional retinal detachment [4]. FEVR can be transmitted in a dominant, recessive, or sex-linked fashion and four genes have been implicated thus far [3]. In this unique case report, we describe a male infant affected by a FEVR-like presentation of homocystinuria that resolved with the treatment of the homocystinuria. 2. Case Report A male infant born in Jackson Memorial Hospital at 36 weeks at 2466 grams via cesarean section for premature rupture of membranes was found to have elevated homocysteine levels (101 mol/L, ref: 4–17 mol/L) on routine labs. He has no other signs of hypercoagulability and was not given supple- mental oxygen. He was referred for genetics evaluation and an ophthalmologic exam at the Bascom Palmer Eye Institute was performed to rule out ectopia lentis. On exam, the patient appropriately reacted to light, ante- rior segment exam and conjunctiva showed no abnormality, nonectopic lens and cornea were clear, and the pupils were equally round and reactive. Dilated fundus exam at 1 week (equivalent of 37 weeks gestation) showed grossly attenuated vessels and avascularity of the retina bilaterally. A retinal angiogram was performed and confirmed the diagnosis of avascularity of the peripheral retina, in a FEVR-like distribu- tion (Figures 1 and 2). Genetic testing showed a heterogeneous unclassified novel missense variant of the cystathionine beta-synthase (CBS) gene, confirming the diagnosis. e patient was then treated with a methionine-free diet, vitamin B6, folic acid, and beta- ine powder. Upon observation, fundus photographs showed regression of the peripheral ridge, and it was noticed that Hindawi Publishing Corporation Case Reports in Ophthalmological Medicine Volume 2014, Article ID 646351, 2 pages http://dx.doi.org/10.1155/2014/646351
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Case ReportFEVR-Like Presentation of Homocystinuria
Lorena A. Montalvo, Vincent D. Venincasa, Hassan A. Aziz,Ditte Hess, and Audina M. Berrocal
Bascom Palmer Eye Institute, University of Miami, 900 NW 17th Street, Miami, FL 33136, USA
Correspondence should be addressed to Audina M. Berrocal; [email protected]
Received 16 September 2014; Accepted 27 October 2014; Published 13 November 2014
Academic Editor: J. Fernando Arevalo
Copyright © 2014 Lorena A. Montalvo et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.
A male infant with a diagnosis of homocystinuria presented with avascularity of the peripheral retina with a ridge on ophthalmicexam, consistent with a FEVR-like manifestation homocystinuria. Upon follow-up and treatment for homocystinuria, the retinalvascularity improved without the need for prophylactic treatment to the peripheral avascular retina.
1. Introduction
Homocystinuria is a rare disorder caused by a defect inmethionine metabolism due to inadequate activity of theenzyme cystathionine beta synthase (CBS) [1]. This results inhyperhomocysteinemia, which is associated with cardiovas-cular disease (i.e., increased risk of abnormal blood clotting),mild cognitive impairment, and dementia. Ocular manifes-tations of homocystinuria include ectopia lentis, glaucoma,macular degeneration, maculopathy, retinal degeneration,and retinal vascular diseases, such as central retinal veinocclusion, branch retinal vein occlusion, and central retinalartery occlusion [2].
Familial exudative vitreoretinopathy (FEVR) is a progres-sive eye disease that affects the vascularization of the periph-eral retina [3]. The characteristic manifestations of FEVRinclude avascularity of the peripheral retina, temporal drag-ging of the vascular arcades, and heterotopia of the macula.Progression of the disease is indicated with subretinal exu-dates and tractional retinal detachment [4]. FEVR can betransmitted in a dominant, recessive, or sex-linked fashionand four genes have been implicated thus far [3].
In this unique case report, we describe a male infantaffected by a FEVR-like presentation of homocystinuria thatresolved with the treatment of the homocystinuria.
2. Case Report
Amale infant born in JacksonMemorial Hospital at 36 weeksat 2466 grams via cesarean section for premature rupture ofmembranes was found to have elevated homocysteine levels(101 𝜇mol/L, ref: 4–17 𝜇mol/L) on routine labs. He has noother signs of hypercoagulability and was not given supple-mental oxygen. He was referred for genetics evaluation andan ophthalmologic exam at the Bascom Palmer Eye Institutewas performed to rule out ectopia lentis.
On exam, the patient appropriately reacted to light, ante-rior segment exam and conjunctiva showed no abnormality,nonectopic lens and cornea were clear, and the pupils wereequally round and reactive. Dilated fundus exam at 1 week(equivalent of 37 weeks gestation) showed grossly attenuatedvessels and avascularity of the retina bilaterally. A retinalangiogram was performed and confirmed the diagnosis ofavascularity of the peripheral retina, in a FEVR-like distribu-tion (Figures 1 and 2).
Genetic testing showed a heterogeneous unclassified novelmissense variant of the cystathionine beta-synthase (CBS)gene, confirming the diagnosis. The patient was then treatedwith a methionine-free diet, vitamin B6, folic acid, and beta-ine powder. Upon observation, fundus photographs showedregression of the peripheral ridge, and it was noticed that
Hindawi Publishing CorporationCase Reports in Ophthalmological MedicineVolume 2014, Article ID 646351, 2 pageshttp://dx.doi.org/10.1155/2014/646351
2 Case Reports in Ophthalmological Medicine
Figure 1: Fluorescein angiogram of the right eye at 1 minute reveal-ing peripheral nonperfusion.
Figure 2: Fluorescein angiogram of the left eye at 1 minute and 17seconds revealing peripheral nonperfusion.
the retina vessels grew from zone 2 to zone 3 forming normalvascularization of the retina. In the last follow-up at 2months,his fundus exam showed a flat retina bilaterally with normalvasculature to the ora serrata.
3. Discussion
Homocystinuria is a condition associated with increasedrisk of primary thrombosis [5]. High levels of homocysteinelead to arteriosclerosis, which is characterized by patchychanges in the arterial wall that lack lipid deposits, thoughtto be secondary to the repair response after repeated muralthrombi [5, 6]. In addition to frank vascular changes, thecystathionine beta-synthase (CBS) enzyme has been shownto play a role in oxidative stress defense and is expressedthroughout the human retina [5, 7].
Dysregulation of vascular growth andmaturation is mostlikely responsible for the FEVR-like retinal manifestationof homocystinuria in this patient. While it is unlikely thattreatment of homocystinuria could reverse arterial changesso quickly, prompt treatment may reduce oxidative stress andallow for a return to normal development with proliferationof the retinal vessels. This was evident when the patientshowed complete vascularization of the peripheral retina onhis final examination.
Although ectopia lentis remains one of themost commonocular abnormalities associated with homocystinuria, a com-plete ocular exam on patients with homocystinuria shouldbe performed to rule out or diagnose retinal abnormalities.Angiography, including wide-field angiography, can be con-sidered to evaluate retinal abnormalities with a vascular com-ponent.
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper.
References
[1] R. M. Homocystinuria, “Review of four cases,” The BritishJournal of Ophthalmology, vol. 55, no. 5, pp. 338–342, 1971.
[2] A. Tawfik, M. Al-Shabrawey, P. Roon et al., “Alterations ofretinal vasculature in cystathionine-beta-synthasemutantmice,a model of hyperhomocysteinemia,” Investigative Ophthalmol-ogy & Visual Science, vol. 54, no. 2, pp. 939–949, 2013.
[3] M. Savarese, E. Spinelli, F. Gandolfo et al., “Familial exuda-tive vitreoretinopathy caused by a homozygous mutation inTSPAN12 in a cystic fibrosis infant,” Ophthalmic Genetics, vol.35, no. 3, pp. 184–186, 2014.
[4] A. M. Joussen, R. S. Gordes, F. A. Heußen, and B. Muller, “Reti-nal exudative disease in childhood: coats disease and familialexudative vitreoretinopathy (FEVR),” Klinische Monatsblatterfur Augenheilkunde, vol. 230, no. 9, pp. 902–913, 2013.
[5] C. Persa, K.Osmotherly, K. C.-W.Chen, S.Moon, andM. F. Lou,“The distribution of cystathionine 𝛽-synthase (CBS) in the eye:implication of the presence of a trans-sulfuration pathway foroxidative stress defense,” Experimental Eye Research, vol. 83, no.4, pp. 817–823, 2006.
[6] K. S. McCully, “Vascular pathology of homocysteinemia: impli-cations for the pathogenesis of arteriosclerosis,” The AmericanJournal of Pathology, vol. 56, no. 1, pp. 111–128, 2013.
[7] S.Markand, A. Tawfik, Y.Ha et al., “Cystathionine beta synthaseexpression in mouse retina,” Current Eye Research, vol. 38, no.5, pp. 597–604, 2013.
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