Ocular Manifestations of Mucopolysacchridosis

ocular Manifestations of MucopolysacchridosisOcular manifestations of mucopolysacchridosisPraddep Sagar Arsikere, Pradeep Venkatesh, Yog Raj SharmaMucopolysaccharidoses(mononuclear phagocyte system) ar a group of disorders caused bytheinherited deficiency of lysosomal enzymes entangled inthemetabolism of glycosaminogly tooshie(GAG),resulting inthewidespread intracellular and extracellular accumulation ofGAG.TypeGeneDeficient enzymeGAG depositedIInheritance shapeHurler syndrome (MPS I-H)IDUA (4p16.3)Alpha-L-iduronidaseDermatan sulfate, heparan sulfateARHurler-Scheie syndrome(MPS I-H/S)IDUA (4p16.3)Alpha-L-iduronidaseDermatan sulfate, heparan sulfateARScheie syndrome (MPS I-S)IDUA (4p16.3)Alpha-L-iduronidaseDermatan sulfate, heparan sulfateARHunter syndrome, severe (MPS II-A)IDS(Xq28)Iduronate sulfataseDermatan sulfate, heparan sulfateXRHunter syndrome, mild (MPS II-B)IDS(Xq28)IduronatesulfataseDermatan sulfate, heparan sulfateXRSanfilippo syndrome A (MPS III-A)SGSH (17q25.3)HeparanN- sulfataseHeparan sulfateARSanfilippo syndrome B (MPS III-B)NAGLU (17q21)Alpha-N-acetylglucosaminidaseHeparan sulfateARSanfilippo syndrome C (MPS III-C)HGSNAT (8p11.1)Heparan-alpha-glucosaminide NacetyltransferaseHeparan sulfateARSanfilippo syndrome D (MPS III-D)GNS(12q14)N-acetyl alpha-glucosamine-6-sulfataseHeparan sulfateARMorquio syndrome A (MPS IV-A)GALNS (16q24.3)N-acetylgalactosamine 6-sulfataseKeratan sulfateARMorquio syndrome B (MPS IV-B)GLB1 (3p21.33)Beta-galactosidaseKeratan sulfateARMaroteaux-Lamy syndrome (MPS VI)ARSB (5q14.1)Arylsulfatase BDermatan sulfateARSly syndrome (MPS VII)GUSB (7q21.11)Beta-glucuronidaseDermatan sulfate, heparan sulfate, Chondroitin sulfateARNatowicz syndrome(MPS IX)HYAL1(3p21)HyaluronidaseAROcular manifestations1. Ocular adnexaEyelid thickeningoccurs out-of-pocket totheaccumulation ofGAG. Hypertelorism has been reported in MPS imagesIII,II andVII. Pseudoproptosis due to shallow orbit has been reported in a patient with MPS VIand MPS II.2. Corne aThe extracellular matrix of corneal stroma contains dermatan sulfate and keratan sulfate in equal proportion. Both dermatan sulfate and keratan sulfate are synthesized by stromal keratocytes. Dermatan sulfate proteoglycans are involved inthecontrol of interfibrillar spacing and inthelamellar adhesion of corneal collagens. Keratan sulfate proteoglycans are involved in the regulation of collagen fibril diameter. Mainly,epithelial cells synthesize heparan sulfate proteoglycans,and they are minor components of cornea.Since dermatan sulfate and keratan sulfate are the major GAGs inthecorneal stroma, corneal involvement is mainly seen in MPS typesI, IV, VI and VII. In corneas of patients with MPS,theexcessive accumulation of dermatan sulfate or keratan sulfate in the form of vacuoles can be seen in epithelial cells, keratocytes, histiocytes and extracellular matrix. An increase inthe sozzled fibril diameter of collagen andanincrease in fibril spacingarenoted in the corneal stroma of pati ents with MPS I. These structural alterations in collagen fibrils whitethorn loan to light scattering. But the corneal clouding is mainly due totheaccumulation of GAGs in all the layers of cornea with enlarged stromal keratocytes.Corneal involvement is typically not seen in type III, as the metabolism of heparan sulfate is impaired in type III and heparan sulfate is not synthesized by stromal keratocytes.Symptoms include gradually progressive painless diminution of visual acuity and light intolerance due to scattering of light. In early cases, fine grey punctuate opacities in anterior stroma are visible. In advanced cases,there is diffuse corneal clouding. Corneal thickness is variable, and it may be increased or normal.Corneal hysteresis is increased. Cornealoedemaoccurs in cases withincreased intra-ocularpressure(IOP).3.Optic nerveGAGsare the major components oftheextracellular matrix oftheoptic nerve head.Proteoglycans containing chondritin sulfate and dermatan sulfate are loca ted in lamina cribrosa, supporting tissues of the optic nerve head like septae, pia. Proteoglycans containing heparan sulfate are located in margins of laminar plates of lamina cribrosa.Theoptic nerve involvement can be due to accumulation ofGAGintheextracellular matrix oftheoptic nerve, narrowing of pores in lamina cribrosa, thickening of duraandnarrowing of bony optic television channelthatleadsto discoedema(pseudopapilloedema). It can also be due to raised intracranial pressure manifesting as true papilloedema.Long-standing axonal compression or papilloedemacan lead to secondary optic atrophy.Theaccumulation of GAG in ganglion cells of retina can lead to axonal decadence and optic atrophy.Optic nerve involvement is to a greater extent commonly seen in typesI, II, VIandVII,as the majorGAGsin optic nerve and lamina cribrosa are dermatan sulfate and chondritin sulfate.Optic nerve involvement is less with type III,as heparan sulfate is located in the margins of lamina cribrosa,and in type IV,as keratan sulfate is not present in the optic nerve head in human.4.GlaucomaThe human trabecular meshwork contains chondroitin sulfate, keratan sulfate, heparan sulfateanddermatan sulfate.Theaccumulation ofGAGin the anterior incision structures can lead tothenarrowing of angle resulting in corking angle closure and chronic angle closure glaucoma. Anterior segmentoptical coherence tomography(OCT)imaging in mucopolysacchridosis suggests crowded anterior segment and increased corneal thickness in type VI thanintype I.Theaccumulation of GAG in trabecular cells can lead to features uniform to open-angle glaucoma.Themeasurement of IOP by Goldmann applanation tonometer may be falsely high due to increased corneal thickness and corneal hysteresis.Thevisualization of angle by gonioscopy may be compromised due to corneal clouding,thus posing difficulty in differentiating open angle from closed angle.Themonitoring of progression and severity of glaucomatous optic neuropathy may be compromised by corneal clouding and discoedema. Anterior segment OCT is a valuable tool intheassessment of angle, curiously in patients with corneal clouding. Ocular responseanalysercan be usedfor theaccurate measurement of IOP in these cases.5. RetinaHeparan sulfate, dermatan sulfate, chondroitin sulfate and hyaluronan are present throughout the retina and choroid. Heparan sulfate is particularly located inthebasement membrane containing structures, the RNFL and RPE. Keratan sulfate is absent intheretina and choroid.GAGsare integral components ofthebasement membrane of retinal microvasculature,and heparan sulfate is the predominant variety. Tapetoretinal degeneration has been reported in MPS typesI,II,III andIV.6.ScleraScleral thickening may lead totheuveal effusion syndrome.Suggested Reading1.Villas-Boas FS, Fernandes Filho DJ, Acosta AX.Ocular findings in patients with mucopolysaccharidosis.Arq Bras Oftalmol201174(6)430434.2.Viestenz A, Shin YS, Viestenz A, Naumann GO.Ocularm anifestation ofmucopolysaccharidosis I-S (Scheiessyndrome).Klin Monbl Augenheilkd2002219(10)745748.