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1 Department of Ophthalmology, Grampian University Teaching Hospitals, Aberdeen, UK
2 Department of Ophthalmology, Gartnavel General Hospital, Glasgow, UK
3 Department of Ophthalmology, Hairmyres General Hospital, East Kilbride, UK
Correspondence to:
T Leslie
Department of Ophthalmology, Grampian University Teaching Hospitals, Aberdeen AB25 2ZN, UK; thorfinnleslie@hotmail.com
Accepted for publication 12 November 2004
Keywords: Morquio syndrome
Mucopolysaccharidoses (MPS) are a group of hereditary storage diseases secondary to deficiencies of lysosomal enzymes. MPS type IV is known as Morquio syndrome.1 In "classic" or type A Morquio syndrome the deficient enzyme is N-acetylgalactosamine-6-sulphate-sulphatase.2 Morquio syndrome has been associated with cataract,3 optic atrophy,4 tapetoretinal pigmentary degeneration,4,5 and corneal clouding.4,6–8 We report a case of type A Morquio syndrome with electron microscopic findings.
Case report
A 38 year old man was referred for consideration of left corneal grafting for progressive corneal haziness of several years’ duration. He was diagnosed with Morquio syndrome in childhood on the basis of severe growth retardation, skeletal dysplasia, and facial dysmorphism. Subsequently, a diagnosis of type A Morquio syndrome was confirmed on enzyme assay of skin fibroblasts. On examination visual acuities were 6/12 right eye and 6/18 left eye. There was bilateral corneal oedema and stromal haze, greater on the left, precluding fundal examination. His intraocular pressures were normal and his angles, although poorly visualised, appeared open.
Following an uneventful left penetrating keratoplasty the host cornea was examined by light, transmission and scanning electron microscopy.
On light microscopy, the basal cells of the epithelium were swollen as a result of oedema but both the epithelium and Bowman’s membrane were of uniform thickness. In paraffin sections the spaces around the keratocytes were enlarged, but this was because of fixation artefact and this abnormality was not seen in the toluidine blue sections. The stroma around the enlarged spaces contained a thin dense border which stained with Alcian blue but not with colloidal iron/periodic acid Schiff or mucicarmine. Descemet’s membrane and the endothelial monolayer were of uniform thickness. In the toluidine blue sections the stroma appeared hypercellular and had a disorderly lamellar pattern. Both the keratocytes and the endothelium contained numerous intracytoplasmic bodies.
At the ultrastructural level, the epithelium contained abnormal inclusion bodies. In areas of the epithelium, the apical portion of the basal cells was packed with small clear membrane-bound vacuoles which decreased in numbers in the wing cell and superficial cell layers. In other sectors the epithelium appeared normal. There were sectors where the basement membrane was markedly thickened and Bowman’s membrane was discontinuous in small areas where fibrocytic and/or inflammatory cells were invading beneath the basal layer. Numerous small unmyelinated nerves were distributed throughout the basal cell layer.
Every keratocyte, to a varying degree, appeared to be involved in the overproduction of mucopolysaccharide and glycolipids. Intracytoplasmic inclusions in the form of multilaminar bodies, fingerprint whorl patterns, fibrillogranular inclusions, small lipid vacuoles, and clear vacuoles were all observed (figs 1 and 2). The collagen bundles in the stromal lamellae appeared normally aligned but scattered throughout the stroma were distended spaces or lacunae occupied by disrupted keratocytes and these distorted the lamellae. In the stromal lamellae around the keratocyte lacunae, there was deposition of an encircling layer of granular material and bundles of wide banded collagen fibres were present in the surrounding corneal stroma (fig 2).
Figure 1 (A) Within the cytoplasm an irregular electron dense mass (arrowhead) is surrounded by concentric membranes (arrow). A granular deposit is present in the stroma around the cell membrane (*) (x120 000). (B) Normal keratocytes were absent from the stroma—the cytoplasm of each cell contained inclusions although the content was variable. Some cells were disrupted by the volume of the inclusions (arrow): many of the cells were surrounded by a layer of electron dense granular material (arrowheads). The corneal lamellae were distorted by the swollen cells (x3800).
Figure 2 (A) In some sectors Bowman’s layer was absent and the epithelium was in contact with fibrous tissue over a thick basement membrane (arrow). Intracytoplasmic bodies were absent from the fibroblasts within the fibrous tissue (arrowheads) (x3800). (B) At lower magnification the inclusions appear to be amorphous in parts, but this represents the concentric lamellar material. The lamellae contain spindle-shaped strips of wide banded collagen (arrowhead). The cell with preserved cytoplasm containing inclusions is surrounded by a layer of electron dense granular material (arrows) (x9600). (C) Descemet’s membrane is of normal thickness. The endothelium contains membranous inclusions, which accumulate to such a level that the cells are cystic (arrow) (x4500). (D) When examined by scanning electron microscopy, the posterior endothelial surface is nodular as a result of the accumulation of intracytoplasmic inclusions. Linear areas of cell disruption are present (x850).
The endothelial cell cytoplasm contained similar abnormalities to those described in the keratocytes with small clear membrane bound vacuoles which had fused to form large empty cytoplasmic spaces causing the cell membranes to collapse. By scanning electron microscopy the endothelial cells possessed a cobblestone appearance because of numerous small nodular bulges on the apical surface but the majority were of normal size and shape and the hexagonal integrity was maintained. Small linear groups of degenerate cells with cytoplasmic disruption were scattered throughout the monolayer. The graft remained clear with no evidence of recurrence 2 years postoperatively with a best corrected visual acuity of 6/6.
Comment
This patient had corneal opacification but none of the other common ocular associations of Morquio syndrome.3–8 As with the two previous studies which investigated the corneal opacification type A Morquio syndrome with electron microscopy.7,8 We found the most obvious abnormality to be mocopolysaccharide inclusions in the form of intracytoplasmic, multilaminar concentric bodies particularly within keratocytes but also affecting the epithelium and endothelium. The degree of keratocyte disruption was striking and possibly related to the late stage of the disease in this case. We confirmed the previous findings of bundles of abnormal collagen fibres, which were present in the corneal stroma around the lacunae6,8 and of areas of epithelial membrane bound vacuoles.7
We identified areas of basement membrane thickening and areas where Bowman’s layer was discontinuous with fibrocytic and/or inflammatory cells invading beneath the basal layer. Numerous small unmyelinated nerves were distributed throughout the basal cell layer. These epithelial changes have not been commented on previously and are possibly secondary to the epithelial oedema which had been identified in this case by light microscopy.
Although early recurrence of opacification has been reported4 the corneal graft in this case remains clear at the 2 year follow up.
References
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