Mucopolysccharidoses : A rare cause for Bilateral cloudy cornea.

Presenting author: Dr. Piyush Madan Co-authors: Dr, Jayshree ikhar GOVERNMENT MEDICAL COLLEGE NAGPUR MAHARASHTRA

Abstract : 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. So we present a case of Mucopolysaccharidosis Type IV, who presented with bilateral corneal clouding and other systemic features of this storage disorder.

Introduction :Mucopolysaccharidoses (MPS) is a rare

multisystemic disorder characterized by deposition of glycosaminoglycans (GAGs) in various tissues of the body, resulting in permanent tissue damage1, 2.

It is a rare cause for bilateral corneal haziness and should be considered as a diffential diagnosis especially in pediatric age group3.

I present a case of Mucopolysaccharidoses type IV for its rarity and variable features.

Case Report :A 5 years old female child presented to

ophthalmology department of our institute with complaints of spontaneous, painless, gradually progressive diminution of vision in both eyes since 5 to 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.

On examination, child had dysmorphic features- 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 (Fig.1)

Ophthalmic examination revealed bilateral pseudo-proptosis. Best corrected V/A (BCVA) in Right eye (RE) was PL+ PR defective, cornea cloudy, stroma showed diffuse haze, pupil semidilated & sluggishly reacting to light,

Fundus showed temporal disc pallor s/o Optic atrophy

In Left eye (LE), BCVA was PL+PR accurate, cornea cloudy and pupil reacting to light, fundus examination revealed: optic disc- CD ratio not comentable, cup full, disk margins blurred s/o disc oedema (Fig.3)

There was no pigmentary retinopathy. Constant 150 exotropia was present in RE. Bilateral IOT

was normal on applanation tonometry. Refraction showed hypermetropia. Pachymetry revealed mild increase in corneal thickness

of both eyes. The facial and skeletal features suggested congenital

developmental syndrome.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, spine showed short stubby small bones, frontal bossing, thick ribs, thickened metaphyses of long bones, spinal thoraco-lumbar kyphosis highly suggestive of MPS (type IV).

2D-ECHO and Color Doppler study & MRI brain was normal.

Urine screening test (Toludine blue dot test) was done and turned out to be positive. Various tests for enzyme activity relevant to different types of MPS. Accordingly the α iduronidase (MPS type I), β galactosidase (GM1 Gangliosidosis), Galactose-6-sulphate sulphatase (MPS Type IV) and Ayrl Sulfatase –B (MPS Type VI) activity was studied.

All the enzymes were reported as normal except Galactose-6-sulphate sulphatase activity, which was found to be below normal i.e. 20nmol/17hr/mg (Normal range 40-170 nmol) thus confirming the diagnosis of MPS type IV (Morquio disease).

Pediatric and orthopedic opinion was sought regarding the management. The option of enzyme replacement therapy was discussed but could not be materialized because of financial constrains.

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 :Mucopolysaccharidoses 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, pulmonary, myocardial, valvular and neurological involvement1,2.

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 e.g. dermatan sulfate, heparan sulfate and keratan sulfate.

There are six major types of Mucopolysaccharidoses, depending on various enzyme deficiencies8,9.

It is often slowly progressive and can cause serious reduction in V/A. Pigmentary retinopathy is reported in all types except types IV, VI & VII.

Optic atrophy is reported occasionally in association with all six mucopolysaccharidoses types. Corneal deposition is usually associated with skeletal dysplasia; similarly mental retardation is associated with pigmentary retinopathies8,9. The detection of GAG’s metabolites in urine along with subnormal enzyme activity in leucocytes confirms the diagnosis7,8,9.

The cardinal clinical features of MPS type IV (Morquio’s Syndrome) were first described by Morquio & Brailsford almost simultaneously1,2.

It is usually associated with prominent skeletal and corneal manifestations, without significant mental retardation or retinal abnormalities as is seen in our case. Detection of keratan sulphate in urine points towards the diagnosis. However The precise enzyme defect is not known, however 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 graft8. 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 life saving9.

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. Presence of corneal opacification or deposits should alert the clinician regarding the possible diagnosis of storage disorder.

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