Ocular Manifestations of Hurler-Scheie Syndrome: Recurrence of Host Disease in the Corneal Transplant

Abstract

Introduction: Hurler-Scheie syndrome is a type of mucopolysaccharidosis I (MPS). In MPS I the decreased activity of alpha-L-iduronidase lysosomal enzyme leads to glycosaminoglycan (GAG) deposition in the intra- and extracellular matrix. Excessive amounts of GAG can accumulate in most layers of the cornea, including epithelial cells, stromal keratocytes, and endothelial cells.

Case presentation: A 25-year-old female patient suffering from Hurler-Scheie syndrome with multiple ocular manifestations is reported. Due to significant bilateral corneal opacification, penetrating keratoplasty was performed on both eyes. Histopathologic examination of the corneal buttons showed disorganized collagen fibers with heterogenous thickness and many granule-containing keratocytes with excessive cytoplasm. Despite receiving enzyme replacement therapy, in vivo confocal microscopy revealed characteristic vacuoles in the basal epithelium and corneal stroma 96 months after transplantation. High resolution anterior segment optical coherence tomography demonstrated hyperreflective opacities superficial and deeper in the stroma which was consistent with recurrence of host disease in the graft.

Conclusion: To the best of our knowledge, this is the first documented Hurler-Scheie syndrome case of recurrence after penetrating keratoplasty demonstrated by in vivo confocal microscopy. Additionally, this patient manifested severe ocular involvement of MPS which might be an explanation of the progressive course of corneal opacification after transplantation.

Keywords: Hurler-Scheie syndrome; In vivo confocal microscopy; Lysosomal storage disease; Mucopolysaccharidosis; Recurrence.

Fig. 1

Preoperative slit lamp photo of the right eye showing diffuse corneal opacification (upper left). B-scan ultrasound demonstrating thickened sclera (3.79 mm) and broad optic nerve (8.41 mm in diameter) (upper right). Fundus photo showing optic disc swelling (lower left). Optical coherence tomography of the macula showing accumulation of granular material in the photoreceptor layer (lower right).

Fig. 2

Corneal stroma showed numerous, periodic acid Schiff and Alcian blue positive granule containing keratocytes with excessive cytoplasm. Hematoxyllin-Eosin, ×40 (left). Periodic acid-Schiff ×40 (middle). Alcian blue, ×40 (right).

Fig. 3

Electron microscopy showing that most of the basal epithelial cells contained vacuoles from which GAG were lost during histological processing (left). Keratocytes have numerous vacuoles (middle), and collagen fibers are randomly arranged. They cross each other, and the diameter of the fibers are inhomogeneous in the outer two-third of the stroma (right).

Fig. 4

Toluidine blue stained thick sections showed fibrogranular material containing vacuoles in the basal epithelial cells (upper left, upper middle) and stromal keratocytes (upper middle, upper right) in the excised corneal button. In vivo confocal corneal microscopy demonstrating accumulation of hyperreflective material in the basal epithelial cells (lower left), Bowman membrane (lower middle), and anterior stroma (lower right) of the graft.

Fig. 5

Slit lamp photo of the clear corneal transplant OD 1 month after penetrating keratoplasty (left). Slit lamp photo of the right eye 96 months after penetrating keratoplasty showing multiple, fine refractile lines in the corneal stroma (middle). Anterior segment optical coherence tomography showing hyperreflective material in the superficial and deeper stroma of the transplanted cornea 8 years after keratoplasty (right).