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

1. Mucopolysccharidoses : A
rare cause for Bilateral
cloudy cornea.
Presenting author: Dr. Piyush Madan
Co-authors: Dr, Jayshree ikhar
GOVERNMENT MEDICAL COLLEGE
NAGPUR MAHARASHTRA

2. 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.

3. 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.

4. 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.

5.  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)

6.  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,

7.  Fundus showed temporal disc pallor s/o Optic atrophy

8.  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)

9.  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).

10.  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).

11.  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.

12.  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.

13.  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.

14.  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.

15.  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.

16.  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.

17.  References :
 Morquio L. Sur une forme dystrophie Osseuse familial. Bull soc Pediatr (Paris)
1929;27: 145-152.
 Brailsford JE. Chondro-osteodystrophy: Roentgenographic and clinical features
of a child with dislocation of vertebrae. Am. J. Surg. 1929;7:404-410.
 Von Noorden GK, Zellweger H., Ponseti IV. Ocular findings of Morquio-Ullrich
disease. Arch Ophthalmol. 1960;64:585-591.
 Langer LO, Carey LS. The roentgenographic features of the KS
mucopolysaccharidisis of Morquio. Am J Roentgenof. 1966;97:1-20.
 Rekhi GS. Morquio syndrome (MPV IV)- A case report. Indian J Ophthalmol.
1991;39:78-81.
 Pagni L, Bartolozzi L, Giacchetti D. Mucopolysaccharidosis : A case report of
Morquio’s type-A disease. Minerva Stomatol. 1992;41(11):527-33.
 Akhtar A, Manandhar S, Ahmad E. Child with mucopolysaccharidosis type IV :
Morquio syndrome. Int J Case Rep Images. 2015; 6(10): 658-660.
 Sugar J. Metabolic disorders of the cornea. In: Kaufman HE, Barron BA,
McDonald MB. The Cornea. 2nd ed. Boston: Butterworth-Heinmann; 1998 : 391-
401.
 Epstein RL. Inborn metabolic disorders and the eye. In: Payman GA, Sanders
DR, Goldberg MF. Principles and practice of Ophthalmology. 1st Indian ed.
Philadelphia: W.B. Saunders Company; 1987 : 1707-1776.