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Ophthalmic Manifestations of Mucopolysaccharidosis Type IS (Scheie Syndrome)

HomeRetina and Vitreous / Retinal Degenerations Associated With Systemic Disease

Title: Ophthalmic Manifestations of Mucopolysaccharidosis Type IS (Scheie Syndrome)

Author: Shane Nau M.S., 4th Year Medical Student, University of Colorado School of Medicine

Photographer: Moran Eye Center Photography (Images 1-3), Lydia Sauer MD (Images 4-5)

Date: February 2016 (Images 1-3), June 2018 (Image 5)

Keywords/Main Subjects: Mucopolysaccharidosis; Lysosome Storage Disorder; Metabolic Disease; Corneal Dystrophy; Retinal Degeneration; Retinitis Pigmentosa; RP; Cystoid Macular Edema; CME; Fluoroscein Angiography; FA; Autofluorescence; AF; Fluoroscein Lifetime Imaging Ophthalmoscope; FLIO

Secondary CORE category:

External Disease and Cornea / Corneal Dystrophies and Ectasias

Pediatric Ophthalmology and Strabismus / Ocular Manifestations of Systemic Disease

Diagnosis: Mucopolysaccharidosis Type IS (Scheie Syndrome)

Brief Case Description:

HPI:

The patient is a 37-year-old female referred to retina clinic for evaluation of bilateral cystoid macular edema (CME) in early 2016. Upon presentation she endorsed blurry vision, 3 years of nyctalopia, and 10 years of floaters and scintillations. Her past ocular history is notable for bilateral corneal dystrophy of unknown etiology, which led to a penetrating keratoplasty (PKP) in her left eye. This procedure was complicated by pupillary-block glaucoma that later required cataract surgery. Despite a corneal transplant in the left eye, her vision remained worse in the left eye compared to the right. OCT imaging of her macula was obtained—revealing bilateral CME.

Her past medical history was significant for hand and foot contractures noted since early childhood, mitral valve stenosis noted in adolescence, severe arthritis, and an umbilical hernia that has since been repaired. She has mildly coarse facial features. She does not have a family history of ocular problems or autoimmune disease. She is allergic to Amoxicillin/Penicillin and presented taking both Ilevro (once daily) and Prednisolone (4X daily) eye drops in addition to 20 mg daily oral Prednisone daily.

Eye Exam: (see Image 1)

Vision: 20/60 cc OD and 20/100 cc OS

Pupils: 5>3, hazy view OD and 7>7, irregular OS

External: Normal OU

Slit Lamp: Diffuse corneal clouding OD, PKP OS clear with peripheral corneal clouding

Fundus Exam: Mild hyperemia of disc, CME, Mottled looking periphery OU

Workup:

CXR: No evidence of Tuberculosis or Sarcoidosis

ECG: Normal

FTA-ABS: Non-reactive

RPR: Non-reactive

ACE: 23 (N)

Lysozyme: <0.70 (N)

Retinal Autoantibodies: (+) for 23-kDA HSP27, 28-kDA, 46-kDA Enolase

MPS Urine Quant.: 12.5 (0-7.1)

MPSI Creatinine: 84 (0)

Total GAG Concentration: 11.5 (0-7.1)

Discussion:

Based on the clinical picture outlined above, it becomes clear that this patient presented with a rare combination of bilateral corneal clouding and retinopathy. Each of these respective findings have lengthy differentials. However, assuming these disease processes share a common etiology, the differential is dramatically narrowed. Using this clinical reasoning, we developed a high index of suspicion for more rare diseases such as the Mucopolysaccharidoses (MPS). Subsequently, a more direct and cost-effective workup was initiated. Quickly thereafter, the MPS labs confirmed the diagnosis of MPS Type IS (Scheie Syndrome) allowing the proper treatment regimen to be initiated.

Mucopolysaccharidosis Type IS (MPS IS, Scheie syndrome) is a type of lysosome storage disorder. Most of the mucopolysaccharidoses are mutations that are inherited in autosomal recessive fashion. With regards to Scheie syndrome, the mutation leads to a deficiency in the enzyme α-L-iduronidase, which is responsible for the degradation of glycosaminoglycans (GAG’s) within the body [1]. Without proper functioning of this GAG degradation process, chronic and progressive deposition of GAG’s throughout the body ensues. The eyes are no exception. According to Ashworth et. al., cytoplasmic membrane-bound vacuoles containing GAG’s are found in most ocular tissue (i.e. cornea, conjunctiva, lens epithelial cells, choroid, ciliary body, RPE, ganglion cells, and trabecular endothelium) in MPS IS patients. This extensive GAG deposition in ocular tissues causes structural and functional changes within the eye.

The following ophthalmic findings have been reported in Scheie Syndrome: proptosis, progressive corneal opacification, corneal edema, open angle glaucoma, pupillary- block glaucoma, cataracts, retinitis pigmentosa, and epiretinal membranes [2]. While the ophthalmic findings are essential to an ophthalmologist, it is contextually important to recognize the other clinical features associated with Scheie syndrome when making the diagnosis. According to Beck et al., the following clinical features of Scheie syndrome are ordered from most to least common: corneal clouding, joint contractures, cardiac valve abnormalities, hernias, carpal tunnel syndrome, and coarse facial features [3]. Each of these findings is found in the majority of Scheie syndrome patients. Perhaps more importantly, the patient in this case had each of these findings at some point in her first three decades of life. Had a provider picked up on her unique clinical history, it is possible she may have been diagnosed at a much earlier age.

Traditionally, ophthalmologic treatment of Scheie syndrome has focused on long-term management with conservatively-timed interventions (i.e. PKP for progressive corneal clouding). However, with the more recent advent of gene and enzyme replacement therapy, new options are becoming available for patients. The patient in this case was started on an experimental enzyme replacement therapy and her CME was tracked with serial OCT imaging. While anecdotal, her CME improved throughout treatment and acutely worsened when the study was ended.

Image/Video: Slit lamp (Image 1), OCT of macula (Image 2), Fluorescein Angiography (Image 3), Autofluorescence (Image 4), Fluorescein Lifetime Imaging Ophthalmoscopy (Image 5)

Description of Images:

Image 1: Slit lamp photo demonstrating diffuse corneal clouding of the right eye.

Image 2: OCT demonstrating cystoid macular edema (CME) with loss of the IS/OS junction surrounding the macula

Image 3: A late fluorescein angiogram photo of the left eye. There are hyper-fluorescent spots surrounding the macula indicating CME as well as significant vascular leakage in the mid-peripheral retina

Image 4: Autofluorescence of the right eye showing a ring-shaped pattern of hyper- and hypo-autofluorescence surrounding the macula.

Image 5: Fluorescein Lifetime Imaging Ophthalmoscopy demonstrating a ring-shaped pattern of prolonged autofluorescence surrounding the macula.

Case Summary:

A 37-year-old patient presented with complaints of blurriness, nyctalopia, and worsened vision in her left eye despite a recent PKP (OS only) for non-specific bilateral corneal dystrophy. She was noted to have bilateral CME and loss of her IS/OS junction on OCT. Autofluorescence and Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO) demonstrated an abnormal ring-shaped pattern around the macula similar to pattern seen with Retinitis Pigmentosa. Operating on the assumption that there was a common etiology for the corneal dystrophy and retinopathy, the diagnosis of mucopolysaccharidoses was suspected and later confirmed with labs. The patient successfully trialed an experimental enzyme replacement therapy and her CME worsened after the funding-based withdrawal of therapy. She has since undergone PKP in right eye as well. She is being followed every 6 months.

Format: Case Report

References:

  1. Thomas JA, Beck M, Clarke JTR, Cox GF. Childhood onset of Scheie syndrome, the attenuated form of mucopolysaccharidosis I. Journal of Inherited Metabolic Disorders. 2010; 33: 421-427.
  2. Ashworth J, et al. Mucopolysacharidoses and the Eye. Survey of Ophthalmology. 2006; 51: 1-17.
  3. Beck M, et al. The Natural History of MPS I: global perspectives from the MPS Registry. Genetics in Medicine. 2014; 16: 759-765.
  4. Andersen KM, Sauer L, Gensure RH, Hammer M, Bernstein PS. Characterization of retinitis pigmentosa using fluorescence lifetime imaging ophthalmoscopy (FLIO). TVST 2018; 7, 20.
  5. Lim, J. et al. Retinitis Pigmentosa. Eye Wiki.  23 May 2018, http://eyewiki.aao.org/Retinitis_Pigmentosa#Disease Accessed 20 June 2018
  6. Van C, Syed NA. Epithelial-Stromal and Stromal Corneal Dystrophies: A Clinicopathologic Review. Revision of [Birkholz ES, Syed NA, Wagoner, MD. Corneal Stromal Dystrophies: A Clinicopathologic Review. Aug. 17, 2009]; EyeRounds.org. August 20, 2015. Available from: http://www.eyerounds.org/cases/43-Corneal-Stromal-Dystrophies.htm

 

Faculty approval by: Akbar. Shakoor, MD

Footer:

Disclosures: None

Identifier: Moran_CORE_25548