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The great masquerade: delayed diagnosis of mucopolysaccharidosis in adulthood
CORRESPONDENCE The great masquerade: delayed diagnosis of mucopolysaccharidosis in adulthood A 54-year-old female was referred to our clinic with visual field loss, nyctalopia, and optic nerve swelling. She also reported mild hearing loss and soft tissue swelling, similar symptoms to when she was diagnosed and operated for a growth hormone–secreting pituitary adenoma 25 years ago. On examination, her acuity was 6/9 bilaterally. She had bilateral optic disc swelling on fundoscopy, but no clinical signs of retinopathy (Fig. 1). Intraocular pressure was normal, and colour vision was intact. Visual field testing showed bilateral paracentral scotomas and a superonasal quadrantic defect in the right eye. Magnetic resonance imaging (MRI) and hormone biochemistry did not show evidence of pituitary tumour recurrence. She was then referred to a specialist eye hospital for diagnostic assessment. Scotopic electroretinogram (ERG) showed an elevated threshold, and both scotopic and photopic ERG showed a reduction in b-wave amplitude. An audiogram showed bilateral mild sensorineural hearing loss. She was thought to have a mild retinopathy, provisionally retinitis pigmentosa (Usher type II). In subsequent years, she was diagnosed with aortic and mitral valve incompetence. She experienced development of weakness and numbness in her hands, with MRI evidence of compressive cervical myelopathy, which recurred even with repeated carpal tunnel releases and cervical decompression. Despite ongoing suspicion of acromegaly, no recurrence was found. On her most recent review, she reported 2 months of cloudy vision. Anterior segment examination demonstrated bilateral flakelike opacities in the posterior corneal stroma (Fig. 2). Genetic testing confirmed the diagnosis of mucopolysaccharidosis I, with heterozygous mutations of the p.Q70x and exon 7 in the IDUA (α-L-iduronidase) gene. The MPSs are a group of inherited lysosomal enzyme disorders that result in accumulation of glycosaminoglycans in tissues. Ocular manifestations include optic disc swelling and atrophy, retinopathy, glaucoma, corneal opacification, and ocular motility abnormalities. In
Fig. 2 — Flakelike opacities in posterior corneal stroma, left eye.
addition to ocular pathology, skeletal, neurologic, cardiac, and/or gastrointestinal abnormalities are often present.1 MPS is usually manifest in childhood, but attenuated forms may not be diagnosed until later in life. Our patient was diagnosed with MPS IS, or Scheie syndrome (after the ophthalmologist Harold Scheie). Her other medical problems are well described in literature to be associated with MPS IS, including carpal tunnel syndrome, cervical myelopathy, deafness, and valvular heart disease. However, some of these symptoms also occur in acromegaly. The ocular manifestations of MPS IS are mild, with late corneal opacification, retinal pigment epithelium degeneration, and optic disc swelling; glaucoma and optic nerve atrophy are rare.2 ERG reduction in b-wave amplitude is seen in MPS.1 Delayed diagnosis of MPS in adulthood is uncommon,3,4 but it happens more often than desirable because of attenuated variants, a low index of suspicion for an uncommon disease, and myriad presentations that may mimic other diseases. In our case, a history of acromegaly contributed to a delay in diagnosis. Undiagnosed MPS leads to ineffective therapy and progression of disease; therefore, early diagnosis is important.3 Prompt enzyme replacement therapy can lead to improvements in respiratory and skeletal symptoms.5 Mucopolysaccharidosis must
Fig. 1 — Bilateral optic disc swelling and gliosis of the left optic nerve head, with no evidence of retinopathy.
Correspondence be considered in atypical ophthalmic presentations with systemic manifestations, even in adults. Emil D. Kurniawan, David P. Francis, Lloyd Bender Department of Ophthalmology, Royal Melbourne Hospital, Melbourne, Victoria, Australia Correspondence to: Emil D. Kurniawan, MBBS: [email protected] REFERENCES 1. Ashworth JL, Kruse FE, Bachmann B, et al. Ocular manifestations in the mucopolysaccharidoses—a review. Clin Experiment Ophthalmol. 2010;38:12-22.
Temporal pellucid marginal degeneration displaying high “with-the-rule” astigmatism Pellucid marginal degeneration is a rare, noninflammatory, progressive form of ectatic degeneration of the cornea, usually bilateral, presenting more often between the third and fifth decades of life. It occurs with a higher incidence in males.1 It usually manifests as a slowly progressive decrease of vision because of the appearance of an “againstthe-rule” astigmatism that is progressive and often irregular. It is diagnosed by slit-lamp biomicroscopy, which shows a peripheral area of stromal thinning separated from the limbus by a healthy corneal area of 2 mm; then it is confirmed topographically. The topography image usually shows the “butterfly wings,” “croissant,” or “crab-claw” image, caused by the vertical flattening of the cornea and the ectatic cornea superior to the area of maximum thinning. Most cases are located in the lower cornea between 4 and 8 hours, but superior locations have been described, as well as 1 nasal form.2–6 We report the case of a 33-year-old female who described a gradual decrease in visual acuity in her right eye for several months. The patient had no relevant personal or family history. Systemic work-up was negative, ruling out any associated autoimmune disease. The visual acuity was 20/50 and improved to 20/30 with –2.25 þ 7.75 901. The refraction with cycloplegic drops confirmed a high “with-the-rule” astigmatism (þ0.25 þ7.5 851). The slit-lamp biomicroscopy showed a temporal thinning at 2 mm from the limbus without any epithelial defects, neovascularization, or lipid deposition (Fig. 1). In the Scheimpflug topography with Pentacam (OCULUS Optikgerate GmbH, Wetzlar, Germany), a “butterfly wings” image was detected in the temporal area (Fig. 2), with an abnormal temporal thinning, a steepening central to the area of maximum thinning, and a significant posterior surface elevation. The diagnosis of temporal pellucid marginal degeneration was made. She had no complaints about her left eye, her visual acuity with no
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2. Ashworth JL, Biswas S, Wraith E, Lloyd IC. Mucopolysaccharidoses and the eye. Surv Ophthalmol. 2006;51:1-17. 3. Hendriksz C. Improved diagnostic procedures in attenuated mucopolysaccharidosis. Br J Hosp Med (Lond). 2011;72:91-5. 4. Bahadir C, Kurtulus D, Cihandide E. Mucopolysaccharidosis type-IS presenting with onset of carpal tunnel syndrome at adolescence. J Clin Rheumatol. 2009;15:402-4. 5. Wraith JE, Clarke LA, Beck M, et al. Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebocontrolled, multinational study of recombinant human alpha-Liduronidase (laronidase). J Pediatr. 2004;144:581-8. Can J Ophthalmol 2013;48:e141–e142 0008-4182/13/$-see front matter Crown Copyright & 2013 Published by Elsevier Inc on behalf of the Canadian Ophthalmological Society. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2013.04.010
optical correction being 20/20. The slit-lamp examination showed no significant corneal thinning. The only remarkable alteration was seen in the Scheimpflug topography with Pentacam camera (Pentacam; OCULUS Optikgerate GmbH) represented by an abnormal elevation of the posterior surface slightly displaced toward the temporal cornea, as well as a significant thinning in the same location (Fig. 3). The cycloplegic refraction revealed only half diopter of “against-the-rule” astigmatism (þ0.5 þ0.5 1721), although a “with-the-rule” cylinder of 0.6 appears in the topography. The case we present is unique because of the location of the stromal thinning in the temporal area, with the appearance of a high “with-the-rule” astigmatism. Most of the cases of pellucid marginal degeneration previously described in the literature presented as an area of inferior stromal thinning with a protrusion of the cornea above the thinned zone causing a high “against-the-rule” cylinder.1 The presence of a high “with-the-rule” astigmatism at the time of
Fig. 1 — Slit-lamp photograph of the right eye showing the peripheral band of thinning in the temporal zone without any epithelial defects, neovascularization, or lipid deposition.
CAN J OPHTHALMOL — VOL. 48, NO. 6, DECEMBER 2013
Fig. 2 — Flakelike opacities in posterior corneal stroma, left eye.
addition to ocular pathology, skeletal, neurologic, cardiac, and/or gastrointestinal abnormalities are often present.1 MPS is usually manifest in childhood, but attenuated forms may not be diagnosed until later in life. Our patient was diagnosed with MPS IS, or Scheie syndrome (after the ophthalmologist Harold Scheie). Her other medical problems are well described in literature to be associated with MPS IS, including carpal tunnel syndrome, cervical myelopathy, deafness, and valvular heart disease. However, some of these symptoms also occur in acromegaly. The ocular manifestations of MPS IS are mild, with late corneal opacification, retinal pigment epithelium degeneration, and optic disc swelling; glaucoma and optic nerve atrophy are rare.2 ERG reduction in b-wave amplitude is seen in MPS.1 Delayed diagnosis of MPS in adulthood is uncommon,3,4 but it happens more often than desirable because of attenuated variants, a low index of suspicion for an uncommon disease, and myriad presentations that may mimic other diseases. In our case, a history of acromegaly contributed to a delay in diagnosis. Undiagnosed MPS leads to ineffective therapy and progression of disease; therefore, early diagnosis is important.3 Prompt enzyme replacement therapy can lead to improvements in respiratory and skeletal symptoms.5 Mucopolysaccharidosis must
Fig. 1 — Bilateral optic disc swelling and gliosis of the left optic nerve head, with no evidence of retinopathy.
Correspondence be considered in atypical ophthalmic presentations with systemic manifestations, even in adults. Emil D. Kurniawan, David P. Francis, Lloyd Bender Department of Ophthalmology, Royal Melbourne Hospital, Melbourne, Victoria, Australia Correspondence to: Emil D. Kurniawan, MBBS: [email protected] REFERENCES 1. Ashworth JL, Kruse FE, Bachmann B, et al. Ocular manifestations in the mucopolysaccharidoses—a review. Clin Experiment Ophthalmol. 2010;38:12-22.
Temporal pellucid marginal degeneration displaying high “with-the-rule” astigmatism Pellucid marginal degeneration is a rare, noninflammatory, progressive form of ectatic degeneration of the cornea, usually bilateral, presenting more often between the third and fifth decades of life. It occurs with a higher incidence in males.1 It usually manifests as a slowly progressive decrease of vision because of the appearance of an “againstthe-rule” astigmatism that is progressive and often irregular. It is diagnosed by slit-lamp biomicroscopy, which shows a peripheral area of stromal thinning separated from the limbus by a healthy corneal area of 2 mm; then it is confirmed topographically. The topography image usually shows the “butterfly wings,” “croissant,” or “crab-claw” image, caused by the vertical flattening of the cornea and the ectatic cornea superior to the area of maximum thinning. Most cases are located in the lower cornea between 4 and 8 hours, but superior locations have been described, as well as 1 nasal form.2–6 We report the case of a 33-year-old female who described a gradual decrease in visual acuity in her right eye for several months. The patient had no relevant personal or family history. Systemic work-up was negative, ruling out any associated autoimmune disease. The visual acuity was 20/50 and improved to 20/30 with –2.25 þ 7.75 901. The refraction with cycloplegic drops confirmed a high “with-the-rule” astigmatism (þ0.25 þ7.5 851). The slit-lamp biomicroscopy showed a temporal thinning at 2 mm from the limbus without any epithelial defects, neovascularization, or lipid deposition (Fig. 1). In the Scheimpflug topography with Pentacam (OCULUS Optikgerate GmbH, Wetzlar, Germany), a “butterfly wings” image was detected in the temporal area (Fig. 2), with an abnormal temporal thinning, a steepening central to the area of maximum thinning, and a significant posterior surface elevation. The diagnosis of temporal pellucid marginal degeneration was made. She had no complaints about her left eye, her visual acuity with no
e142
2. Ashworth JL, Biswas S, Wraith E, Lloyd IC. Mucopolysaccharidoses and the eye. Surv Ophthalmol. 2006;51:1-17. 3. Hendriksz C. Improved diagnostic procedures in attenuated mucopolysaccharidosis. Br J Hosp Med (Lond). 2011;72:91-5. 4. Bahadir C, Kurtulus D, Cihandide E. Mucopolysaccharidosis type-IS presenting with onset of carpal tunnel syndrome at adolescence. J Clin Rheumatol. 2009;15:402-4. 5. Wraith JE, Clarke LA, Beck M, et al. Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebocontrolled, multinational study of recombinant human alpha-Liduronidase (laronidase). J Pediatr. 2004;144:581-8. Can J Ophthalmol 2013;48:e141–e142 0008-4182/13/$-see front matter Crown Copyright & 2013 Published by Elsevier Inc on behalf of the Canadian Ophthalmological Society. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2013.04.010
optical correction being 20/20. The slit-lamp examination showed no significant corneal thinning. The only remarkable alteration was seen in the Scheimpflug topography with Pentacam camera (Pentacam; OCULUS Optikgerate GmbH) represented by an abnormal elevation of the posterior surface slightly displaced toward the temporal cornea, as well as a significant thinning in the same location (Fig. 3). The cycloplegic refraction revealed only half diopter of “against-the-rule” astigmatism (þ0.5 þ0.5 1721), although a “with-the-rule” cylinder of 0.6 appears in the topography. The case we present is unique because of the location of the stromal thinning in the temporal area, with the appearance of a high “with-the-rule” astigmatism. Most of the cases of pellucid marginal degeneration previously described in the literature presented as an area of inferior stromal thinning with a protrusion of the cornea above the thinned zone causing a high “against-the-rule” cylinder.1 The presence of a high “with-the-rule” astigmatism at the time of
Fig. 1 — Slit-lamp photograph of the right eye showing the peripheral band of thinning in the temporal zone without any epithelial defects, neovascularization, or lipid deposition.
CAN J OPHTHALMOL — VOL. 48, NO. 6, DECEMBER 2013