Morquio Syndrome in Two Siblings : A Case Report

Morquio syndrome is a rare inherited autosomal recessive disorder characterized by the accumulation of mucopolysaccharides (glycosaminoglycans) in various body tissues. It is rare cause of dwarfism. Many pediatricians therefore are unlikely to see this case hence may miss the diagnosis due to lack of experience. With this view we report two siblings with this dwarfism highlighting the classical clinical and radiological presentation.

A six year old female child was brought to the out patient department of Manipal Teaching Hospital with symptoms of lower respiratory tract infection.On examination she had akward looking facies with frontal bossing and bilateral proptosis (Fig 1) hence was admitted for further evaluation.She was disproportionately short (short trunk and long limbs (Fig 1 )), with height 95 cm (Expected height 114cm (Height / age 83% moderate stunting according to Waterlow classifi cation).She also had other skeletal abnormalities like pectus carinatum, short neck, knock -knees, kyphosis, joint hypermobility, projecting jaw, broad mouth and fl at feet.She had a younger brother having similar features.Her parents had a consanguineous marriage.Both parents were normal looking.The parents never thought that their children had any problems as both looked alike and their intelligence and development was age appropriate (Fig 2).Skeletal survey of both siblings revealed features of MPS -X-ray of the skull showed large skull with a J-shaped sella.Atlantoaxial subluxation was seen in radiographs of the cervical spine (Fig 3).Oar-shaped ribs were seen in AP and lateral views of the chest X-ray (Fig 4).Standing AP and lateral views of lower thoracic and lumbar vertebrae revealed fl at and irregular vertebral bodies, along with anterior beaking of the vertebral bodies (Fig 5).The pelvic radiograph showed fl ared ilia with inferior constriction ("wine-glass" shape) (Fig 6).X-ray of knees hand and forearm in AP view showed genu valgus (Fig 7), metaphyseal expansion of long bones, and tapering of the proximal phalanges (Fig 8 ) respectively.Besides skeletal abnormalities they also had hepatomegaly, Corneal clouding and congenital cataract.On cardiovascular evaluation the sister had mild to moderate mitral regurgitation.Bone marrow biopsy revealed increased foamy histiocytes with large vacuolated cytoplasm which was consistent with the diagnosis of MPS type IV, Morquio syndrome (Fig 9).Due to the unavailability of other investigations like urinary keratine level, Fibroblast culture of a skin biopsy for reduced activity of N-acetyl-galactosamine-6-sulfatesulfatase and genetic study could not be performed.

Discussion
Morquio syndrome (mucopolysaccharidosis type IV; MPS IV) is a rare mucopolysaccharide storage disease that exists in two forms (Morquio syndromes A and B) and occurs because of a defi ciency of the enzymes N-acetyl-galactosamine-6-sulfatase and beta-galactosidase, respectively 1,2 It was fi rst described simultaneously by Morquio 3 , a pediatrician in Uruguay and Brailsford 4 , a radiologist in England in year 1929.The incidence is unknown but estimates have ranged from 1 case per 75,000 people in Northern Ireland to 1 case per 200,000 people in British Columbia 2 .Defi ciency of above mentioned enzymes lead to the accumulation of mucopolysaccharides or glycosaminoglycans (GAGs) in the body, giving rise to various symptoms.Dermatan sulfate, heparan sulfate, keratan sulfate (KS), and chondroitin sulfate are the main GAGs in tissues 5 .Clinical features vary depending on the tissue distribution of the affected substrate and the degree of enzyme defi ciency.In Morquio syndrome, the GAG which is defective is KS.This defective degradation of KS occurs due to defi ciency of either N-acetyl-galactosamine-6-sulfatase (GALNS gene) in MPS IVA or beta-galactosidase (GLB1 gene) in MPS IVB 5 .KS is predominantly found in cartilage and cornea and these are the major organs affected in Morquio syndrome.In our case also these were the major organs involved.The metabolism of Heparan and dermatan sulfate which has more generalized tissue distribution is normal in Morquio syndrome.This is the reason why patients with Morquio syndrome does not have mental retardation.Both the siblings in the above case had normal intelligence.Compared to other MPS, Morquio syndrome tend to have greater skeletal manifestations and spine involvement like scoliosis, kyphosis, hyperlordosis and severe gibbus, fl aring of the lower ribs as well as platyspondyly, pectus carinatum,   and ligamentous laxity, odontoid hypoplasia, a striking short trunk dwarfi sm, short neck, fl at feet, genu valgus, projecting jaw, broad mouth 6,7 .Additional physical features are hearing defects, carious teeth, growth retardation, hepatomegaly, and aortic and/or mitral regurgitation 8,9 .
All these features were present in our case except for hearing which was normal.No clear clinical differentiation between Morquio syndrome type IVA and IVB exists.The clinical features of MPS IV-B are usually fewer and milder than those associated with MPS IV-A 10 .With this view possibly our case is Morqio syndrome type IV-B.Patients with Morquio syndrome have a predisposition to pulmonary infection because of progressive truncal deformity and immobility.Earlyonset coronary heart disease and valve thickening (aortic and mitral) with resultant cardiac dysfunction are also described in these patients 8 .Pulmonary infection was observed in our case.Other rare abnormalities include lens opacities, retinopathy, optic atrophy, and pseudoexophthalmos 11 .Lens opacities and pseudoexophthalmos was present in both our cases.
Imaging fi ndings in Morquio is very helpful for diagnosis.To descri be the skeletal fi ndings Husler coined the term dysostosismultiplex 12 .The radiological features as described above in our case are consistent with dysostosis multiplex.The diagnosis is confi rmed by direct enzymatic assay in leukocytes or fi broblasts 13 .As this facility was not available in our setup we could not perform this test.The Histological fi nding shows engorged unmetabolized GAG in lysosomes.These appear as vacuoles or inclusion bodies in cells such as lymphocytes, hepatocytes, corneal epithelium, and neurons 14 .
Treatment is only palliative for Morquio syndrome.Potential strategies -which are currently at different levels of development, include enzyme replacement, gene therapy, and allogenic bone marrow transplantation in which engrafted cells provide the normal enzyme 15 .

Conclusion
This gives a guideline to suspect diagnosis of mucopolsaccharidosis.We strongly recommend the importance of performing careful clinical examination and proper investigations for such cases.

Fig1:
Fig1: Patient having abnormal facies and disproportionate short stature (photographed with permission of mother).

Fig 4 :
Fig 4: X-Ray of chest (PA view) Showing Oar-shaped ribs of the patient.

Fig 5 :
Fig 5: X-ray vertebrae (lateral view) of patient showing fl attening and irregularity of the vertebral bodies with anterior beaking.

Fig 3 :
Fig 3: X-Ray of skull (Lateral view) showing large skull with a J-shaped sella of the patient

Fig 7 :
Fig 7: X-Ray both knees and leg (AP view) showing genu valgus in the patient.

Fig 8 :
Fig 8: X -Ray both hands (AP view) showing metaphyseal expansion of long bones with cortical thinning, and tapering of the proximal phalanges in the patient.