|Year : 2017 | Volume
| Issue : 2 | Page : 93-96
Mucopolysaccharidoses: A rare cause for bilateral cloudy cornea
Jayshri Vipin Ekhar1, Piyush Ashok Madan2, Samreen Ayubi1, Dipti Solanki1
1 Department of Ophthalmology, Government Medical College, Nagpur, Maharashtra, India
2 Department of Ophthalmology, J. N. Medical College, Wardha, Maharashtra, India
|Date of Submission||18-Oct-2015|
|Date of Acceptance||01-Dec-2016|
|Date of Web Publication||25-Apr-2017|
Jayshri Vipin Ekhar
Flat No. 201, B-wing, Poonam Heights, Pande Layout, Khamla, Nagpur - 440 025, Maharashtra
Source of Support: None, Conflict of Interest: None
There are many different causes for corneal clouding/opacification which include both local ophthalmic causes as well as systemic causes. Mucopolysaccharidosis is a rare cause. Hence, we present a case of mucopolysaccharidosis type IV, who presented with bilateral corneal clouding and other systemic features of this storage disorder.
Keywords: Corneal clouding, enzyme deficiency, mucopolysaccharidosis
|How to cite this article:|
Ekhar JV, Madan PA, Ayubi S, Solanki D. Mucopolysaccharidoses: A rare cause for bilateral cloudy cornea. J Clin Ophthalmol Res 2017;5:93-6
|How to cite this URL:|
Ekhar JV, Madan PA, Ayubi S, Solanki D. Mucopolysaccharidoses: A rare cause for bilateral cloudy cornea. J Clin Ophthalmol Res [serial online] 2017 [cited 2020 Mar 30];5:93-6. Available from: http://www.jcor.in/text.asp?2017/5/2/93/205180
Mucopolysaccharidoses (MPS) is a rare multisystem disorder characterized by deposition of glycosaminoglycans (GAGs) in various tissues of the body, resulting in permanent tissue damage., It is a rare cause for bilateral corneal haziness and should be considered as a differential diagnosis, especially in pediatric age group. We present a case of MPS type IV for its rarity and variable features. This report also stresses the multisystem involvement and need of multidisciplinary approach in diagnosis and management of MPS.
| Case Report|| |
A 5-year-old female child presented to Ophthalmology Department of our institute with complaints of spontaneous, painless, gradually progressive diminution of vision in both eyes for 5–6 months. It was not associated with photophobia, watering, or redness of eyes. Birth history: second child of consanguineous marriage, full-term, normal birth weight, vaginal hospital delivery. Elder brother was developmentally normal. Family tree was traced and was not significant.
On examination, child had dysmorphic features such as frontal bossing, hypertelorism, saddle nose, low-set ears, macroglossia, short stature, short neck, kyphosis of lumbar spine, pigeon chest, widening of wrist, bowing of legs, doubling of malleoli, abdominal distension, umbilical hernia, noisy breathing, and hirsutism [Figure 1]. Ophthalmic examination revealed bilateral pseudoproptosis. Best-corrected visual acuity (BCVA) in the right eye (RE) was perception of light (PL) + projection of rays (PR) defective, cornea cloudy; stroma showed diffuse haze, pupil semidilated, and sluggishly reacting to light [Figure 2]; fundus showed temporal disc pallor suggestive of optic atrophy [Figure 3]. In the left eye (LE), BCVA was PL + PR accurate, cornea cloudy, and pupil reacting to light; fundus examination revealed cup disc ratio not commentable, cup full, disk margins blurred suggestive of disc edema [Figure 4]. There was no pigmentary retinopathy in both the eyes. Constant 15° exotropia was present in RE. Ocular movements were full and fixation was by LE. Bilateral intraocular pressure was normal on Perkins applanation tonometry. Refraction showed hypermetropia. Pachymetry revealed mild increase in corneal thickness of both eyes (RE: 564 μm; LE: 560 μm).
|Figure 1: Patient showing features of facial dysmorphism, short stature, abdominal distension, umbilical hernia, bowing of legs, widening of wrist, and kyphosis|
Click here to view
The facial and skeletal features suggested congenital developmental syndrome; hence, a pediatric reference was done and a diagnosis of storage disorder (MPS) was suspected. Blood counts, glucose levels, kidney functions, liver functions, and electrolytes were normal. Ultrasonography of abdomen showed mild hepatomegaly. Radiology of skull, face, chest, long bones, and spine showed short stubby small bones, frontal bossing, thick ribs, thickened metaphyses of long bones, spinal thoracolumbar kyphosis highly suggestive of MPS (type IV). Two-dimensional echo and color Doppler study and magnetic resonance imaging brain were normal. With strong suspicion of MPS, the urine screening test (toluidine blue dot test) was done and turned out to be positive. We went ahead with various tests for enzyme activity relevant to different types of MPS. Accordingly, α-iduronidase (MPS type I), β-galactosidase (GM1 gangliosidosis), galactose-6-sulfate sulfatase (MPS type IV), and aryl sulfatase-B (MPS type VI) activity were studied. All the enzymes were reported as normal except galactose-6-sulfate sulfatase activity, which was found to be below normal, i.e., 20 nmol/17 h/mg (normal range 40–170 nmol) thus confirming the diagnosis of MPS type IV (Morquio disease).
Pediatric and orthopedic opinion were sought regarding the management. The option of enzyme replacement therapy was discussed but could not be materialized because of financial constraints. There was no obvious neurological deficit at present, so there was no urgent orthopedic intervention needed. As there was bilateral optic nerve compromise, the surgical correction of corneal haziness, i.e., penetrating keratoplasty, was not considered. The patient was kept under long-term follow-up so that necessary management can be planned as and when needed.
| Discussion|| |
Cloudy corneas are features of metabolic disorders such as MPS and mucolipidoses. MPS are inherited lysosomal storage diseases characterized by deficiency of enzymes involved in the degradation of GAGs. GAGs are long chain complex carbohydrates helping in formation of bone, cartilage, tendons, corneas, skin, and connective tissues. As a result, GAGs slowly accumulate in various tissues of the body, resulting in permanent cellular damage. Common clinical presentations include facial and skeletal abnormalities, corneal stromal infiltration, pigmentary retinopathy, optic atrophy, hepatosplenomegaly, and pulmonary, myocardial, valvular, and neurological involvement., All these syndromes are autosomal recessive, with the exception of the X-linked recessive Hunter syndrome. Patients with MPS excrete one or more of the following chemicals (GAGs) into their urine, for example, dermatan sulfate, heparan sulfate, and keratan sulfate.
There are six major types of MPS, depending on various enzyme deficiencies [Table 1].,,,,, Although clinical and morphological findings are overlapping, certain ophthalmological findings help in differentiation. Corneal depositions occur in all types of MPS except type II and III. These depositions are mostly microscopic (stippled areas); however, in type I (Hurler's disease and Scheie's disease), the depositions are often associated with corneal clouding. It is often slowly progressive and can cause serious reduction in visual acuity. Pigmentary retinopathy is reported in all types except types IV, VI, and VII. Optic atrophy is reported occasionally in association with all six MPS types. Corneal deposition is usually associated with skeletal dysplasia; similarly, mental retardation is associated with pigmentary retinopathies., The detection of GAG's metabolites in urine along with subnormal enzyme activity in leukocytes confirms the diagnosis.,,
The cardinal clinical features of MPS type IV (Morquio's syndrome) were first described by Morquio and Brailsford almost simultaneously., It is usually associated with prominent skeletal and corneal manifestations, without significant mental retardation or retinal abnormalities as seen in our case. The roentgenographic features of this disease in our case matched with those reviewed by Langer & Carey. Detection of keratan sulfate in urine points toward the diagnosis. Although the precise enzyme defect is not known, it is thought to be a sulfatase, either for N-acetyl galactosamine-6-sulfate or for galactose-6-sulfate.
Treatment options include enzyme replacement therapy and hematopoietic stem cell transplantation. The corneal lesions are sometimes amenable to penetrating keratoplasty, unless impairment of the patient's mental status or retinal or optic nerve abnormalities precludes visual improvement. The prognosis for successful keratoplasty is guarded as abnormal storage material may accumulate in the graft. In MPS type IV, progressive neurological manifestation secondary to spinal malformations and resulting medullary compression is mostly responsible for early deaths. In these patients, timely spinal surgeries can be lifesaving.
| Conclusion|| |
MPS is a rare multisystem disorder, often diagnosed clinically and radiologically. The diagnosis can be confirmed by relevant enzyme assays. Ophthalmological manifestations help in typing the disease. The presence of corneal opacification or deposits should alert the clinician regarding the possible diagnosis of storage disorder.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Morquio L. Surune forme dystrophie osseuse familial. Bull Soc Pediatr (Paris) 1929;27:145-52.
Brailsford JE. Chondro-osteodystrophy: Roentgenographic and clinical features of a child with dislocation of vertebrae. Am J Surg 1929;7:404-10.
Von Noorden GK, Zellweger H, Ponseti IV. Ocular findings in Morquio-Ullrich's disease. With report of two cases. Arch Ophthalmol 1960;64:585-91.
Langer LO Jr., Carey LS. The roentgenographic features of the KS mucopolysaccharidosis of Morquio (Morquio-Brailsford's disease). Am J Roentgenol Radium Ther Nucl Med 1966;97:1-20.
Rekhi GS. Morquio syndrome (MPV IV) – A case report. Indian J Ophthalmol 1991;39:78-81.
] [Full text]
Pagni L, Bartolozzi L, Giacchetti D. Mucopolysaccharidosis. A case report of Morquio's type-A disease (MPS IV-A). Minerva Stomatol 1992;41:527-33.
Akhtar A, Manandhar S, Ahmad E. Child with mucopolysaccharidosis type IV: Morquio syndrome. Int J Case Rep Images 2015;6:658-60.
Sugar J. Metabolic disorders of the cornea. In: Kaufman HE, Barron BA, McDonald MB, editors. The Cornea. 2nd
ed. Boston: Butterworth-Heinmann; 1998. p. 391-401.
Epstein RL. Inborn metabolic disorders and the eye. In: Payman GA, Sanders DR, Goldberg MF, editors. Principles and Practice of Ophthalmology. 1st
Indian Edition. Philadelphia: W.B. Saunders Company; 1987. p. 1707-76.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]