OPHTHALMOLOGICAL MANIFESTATIONS IN FABRY'S DISEASE. FOUR CLINICAL CASES SHOWING DEFICIENT ALPHA-GALACTOSIDASE-A ACTIVITY

Size: px

Start display at page:

Download "OPHTHALMOLOGICAL MANIFESTATIONS IN FABRY'S DISEASE. FOUR CLINICAL CASES SHOWING DEFICIENT ALPHA-GALACTOSIDASE-A ACTIVITY"

Augusta Owen
8 years ago
Views:

1 ARCH SOC ESP OFTALMOL 2008; 83: SHORT COMMUNICATION OPHTHALMOLOGICAL MANIFESTATIONS IN FABRY'S DISEASE. FOUR CLINICAL CASES SHOWING DEFICIENT ALPHA-GALACTOSIDASE-A ACTIVITY MANIFESTACIONES OFTALMOLÓGICAS EN LA ENFERMEDAD DE FABRY. A PROPÓSITO DE 4 CASOS CON ACTIVIDAD DEFICIENTE DE a-galactosidasa A RODRÍGUEZ-GONZÁLEZ-HERRERO ME 1, MARÍN-SÁNCHEZ JM 2, GIMENO JR 3, MOLERO-IZQUIERDO C 4, DE-CASAS-FERNÁNDEZ A 4, RODRÍGUEZ-GONZÁLEZ-HERRERO B 4, SAN-ROMÁN I 4, LOZANO J 4, DE-LA-MORENA G 3, LLOVET-OSUNA F 2 ABSTRACT Case report: Fabry s disease is an illness produced by an alteration in the catabolism of the glycosphingolipids. We report ophthalmologic findings in 4 people, detected after 113 patient evaluations from an analytical, cardiological and genetic point of view. Discussion: Fabry s disease is uncommon and shows variable ophthalmologic affectation. Some patients with Fabry s disease do not present ocular affectation, while, on the other hand, healthy carriers with important ocular alterations have been described. The deposit of glycosphingolipids produces affectation at the corneal, crystalline, vascular and retinal levels. The vascular alterations affect not only the veins but also the arteries, as we report in our patients (Arch Soc Esp Oftalmol 2008; 83: ). Key words: Fabry s Disease, alpha-galactosidase- A, vasculopathy. RESUMEN Caso clínico: La enfermedad de Fabry es una enfermedad producida por una alteración en el catabolismo de los glucoesfingolípidos. Se muestran las alteraciones oftalmológicas de cuatro pacientes detectados tras evaluar desde el punto de vista analítico, cardiológico y genético a 113 enfermos. Discusión: La enfermedad de Fabry es una enfermedad infrecuente con afectación oftalmológica inconstante existiendo enfermos con Fabry sin afectación ocular y portadores sanos, con importantes alteraciones oculares. El depósito de glucoesfingolípidos produce afectación a nivel corneal, cristaliniano, vascular y retiniano. Las alteraciones vasculares afectan no sólo a las venas sino también a las arterias como mostramos en nuestros pacientes. Palabras clave: Enfermedad de Fabry, alfa-galactosidasa A, vasculopatía. Received: 28/5/07. Accepted: 21/11/08. Virgen de la Arrixaca University Hospital. Murcia University. Murcia. Spain 1 Ph.D. in Medicine. Associate University Professor. Ophthalmology Specialist. 2 Graduate in Medicine. Ophthalmology Specialist. 3 Ph.D. in Medicine. Ophthalmology Specialist. 4 Graduate in Medicine. Paper presented at the LXXXII Congress of S.E.O. (A Coruña 2006). Correspondence: M.ª Elena Rodríguez González-Herrero Edificio Avenida Avda. Europa, 26, 1.ª Esc. 3.º B Murcia, Spain mariaelenargh@hotmail.com

A PROPÓSITO DE 4 CASOS CON ACTIVIDAD DEFICIENTE DE a-galactosidasa A RODRÍGUEZ-GONZÁLEZ-HERRERO ME 1, MARÍN-SÁNCHEZ JM 2, GIMENO JR 3, MOLERO-IZQUIERDO C 4, DE-CASAS-FERNÁNDEZ A 4,

2 RODRÍGUEZ-GONZÁLEZ-HERRERO ME, et al. INTRODUCTION Fabry s disease is a rare recessive systemic disease linked to X, produced by an alteration in the catabolism of glycosphingolipids due to a deficient activity of the lysosomal a-galactosidase A enzyme (AaGA; fig. 1). With a prevalence of 1/ cases, it produces alterations in different organs, mainly the kidney and at the neurological, cardiologic, dermatological and ophthalmological level (1). This short communication presents the ophthalmological expressions in four patients (three affected by Fabry s disease and one carrier) that were detected after cardiological studies in 113 patients affected by hypertrophic myocardiopathy (HMC) by the Cardiology Service of the Virgen de la Arrixaca Hospital. For the diagnosis, levels of AaGA <30% for males and <50% for females were taken as pathological. In addition, a genetic study of the Xq22 chromosome region was performed for each patient. Case 1 A 52 year-old male affected by Fabry s disease who is a member of family H171 (graph 1). He exhibits a corrected visual acuity (CVA) of 0.9 in both eyes (BE), bilateral nasal pterigion, dilatation of conjunctival vessels (fig. 2), Cornea verticillata (fig. 3), pigmentary mobilization at the level of the posterior pole with increased pigmentation above the papilla and increase of arterial and venous and vascular tortuosity confirmed by FAG AFG (fig. 4). The remainder of the ophthalmological exploration was normal. CASE REPORTS The Ophthalmological Service of the Virgen de la Arrixaca University Hospital assessed 4 patients (three affected by Fabry s disease and one carrier). Patient 1 (p1) exhibited a detection in exon 7 ( of GAG) and three patients (p2, p3, p4) exhibited an alteration in exon 6 (Asp313Tyr). Diagram 1: Showing the family tree of family H171. Fig. 1: Scheme of the catabolism of Globotriosylceramide (GL3) to Lactosylceramide by means of the a-galactosidase A enzyme. Fig. 2: Conjunctival vascular alterations, with irregular width and vascular ectasiae in patient ARCH SOC ESP OFTALMOL 2008; 83:

a-galactosidase A enzyme (AaGA; fig. 1).

3 Ophthalmological Manifestations In Fabry s Disease Fig. 3: Epithelial corneal deposits of ceramides in patient 1. Case 2 An 81 year-old male diagnosed with EPOC, Fabry s disease and HMC. The patient is a heart pacer user and is a member of family H202. CVA is of 0.3 RE. Amaurosis in LE secondary to traumatism. No signs of Fabry s disease were detected. Fig. 4: Angiography (FAG) showing the increased arterial and venous tortuosity at the level of the posterior pole of the RE in patient 1. Case 3 A 45 year-old healthy male, carrier of the alphagalactosidase mutation, member of family H90 (graph 2). The ophthalmological assessment shows a CVA of 0.8 in RE and 0.9 in LE, dilatation of conjunctival vessels (fig. 5), lackluster cornea with Diagram 2: Showing the family tree of family H90. ARCH SOC ESP OFTALMOL 2008; 83:

4: Angiography (FAG) showing the increased arterial and venous tortuosity at the level of the posterior pole of the RE in patient 1.

4 RODRÍGUEZ-GONZÁLEZ-HERRERO ME, et al. reduced transparency and crystal-like dotted opacities in the equator, pigmentary mobilization at the level of the posterior pole and equatorial, with alterations of the retinal pigmentary epithelium. Case 4 Fig. 5: conjunctival vascular alterations of patient 3. A 56 year-old male, affected by Fabry s disease and HMC, member of family H90 (graph 2). The ophthalmological exploration revealed a CVA of 1 in both eyes, slight bilateral phakosclerosis, ectasiae in conjunctival vessels, cornea verticillata and pigmentary alterations at the level of the posterior pole in the eye fundus and FAG (fig. 6). Fig. 6: Retinographies and FAG of patient showing pigmentary epithelium alterations at the macular level in both eyes. Note the normal width and regularity of the vessels. 716 ARCH SOC ESP OFTALMOL 2008; 83:

Case 4 Fig. 5: conjunctival vascular alterations of patient 3. A 56 year-old male, affected by Fabry s disease and HMC, member of family H90 (graph 2).

5 Ophthalmological Manifestations In Fabry s Disease DISCUSSION Fabry s disease is an infrequent disease that causes multiple pathologies at the systemic and ophthalmological level. The patients described above exhibited cardiological alterations undistinguishable from patients affected by hypertrophic myocardiopathy with normal AaGA, for which reason the existence of ophthalmological alterations compatible with Fabry s disease supports the diagnostic. Ophthalmological involvement is not constant. Some Fabry s disease patients may not have eye disorders (patient 2) while healthy patients who carry Fabry s disease may have characteristic ophthalmological expressions (patient 3). The ophthalmological pathologies described in literature comprise vascular alterations, periorbitary edema, Cornea Verticillata, cataracts, peripheral retinal pigmentations, papilledema, occlusion of the central retinal artery, optical atrophy, dischromatopsia, nistagmus and internuclear ophthalmoplegia (1-2,4). Corneal involvement is most frequent, with the deposit of glycosphingolipids between the basal membrane of the corneal epithelium and Bowman s membrane being characteristic, producing the corneal involvement in the form of Cornea Verticillata, which is also observed in patients affected by Tangier disease, striated melanokeratosis, Melkersson-Rosenthal syndrome and secondary to medications such as Amiodarona or Chlorokine. As patient 1 was in chronic treatment with Amiodarona, he was called in for an ophthalmological checkup six months after discontinuing the treatment, where the exploration exhibited Cornea Verticillata in the stage referred above. This suggests that said deposits could be secondary to Fabry s disease. The characteristic lens involvement consists in opacification of lens sutures at the posterior level, producing Fabry s disease cataracts. There are other lens alterations such as phakosclerosis and nonspecific lens deposits and opacities. Vascular conjunctival and retinal lesions are part of the systemic involvement of small vessels in Fabry s disease (3,5) and is secondary to intra-cytoplasmic deposits in the vascular endothelium. Aneurismatic dilatations, angulations and segmentation of conjunctival vessels occurred in 60% of Fabry s disease patients, but have not been referred in carriers of the disease or affecting the retinal arteries as in the above patients. Fabry s disease is an infrequent disease. However, detecting the ophthalmological involvement caused by this disease facilitates the early diagnosis thereof and allows early treatment, thus avoiding irreversible damages caused by the GL-3 deposits. REFERENCES 1. Iester M, Sodi A, Ocella C, Vittone P. Ocular finding in Fabry s disease. Contrib Nephrol 2001; 136: Orssaud C, Dufier J, Germain D. Ocular manifestations in fabry disease: a survey of 32 hemizygous male patients. Ophthalmic Genet 2003; 24: Dichgans M. A new cause of hereditary small vessel disease. Angiopathy of retina and brain. Neurology 2003; 60: Nguyen TT, Gin T, Nicholls K, Low M, Galanos J, Craford A. Ophthalmological manifestations of fabry disease: a survey of patiens at the Royal Melbourne Fabry disease treatment centre. Clin Exp Ophthalmol 2005; 33: Sodi A, Ioannidis A, Mehta A, Davey C, Beck M, Pitz S. Ocular manifestations of Fabry disease: data from the Fabry Outcome Survey. Br J Ophthalmol 2007; 91: ARCH SOC ESP OFTALMOL 2008; 83:

ophthalmological alterations compatible with Fabry s disease supports the diagnostic. Ophthalmological involvement is not constant.

Visual Disorders in Middle-Age and Elderly Patients with Diabetic Retinopathy

Medical Care for the Elderly Visual Disorders in Middle-Age and Elderly Patients with Diabetic Retinopathy JMAJ 46(1): 27 32, 2003 Shigehiko KITANO Professor, Department of Ophthalmology, Diabetes Center,