Ocular Manifestations of Mucopolysacchridosis

visual Manifestations of Mucopolysacchridosisocular manifestations of mucopolysacchridosisPraddep Sagar Arsikere, Pradeep Venkatesh, Yog Raj SharmaMucopolysaccharidoses( system of macrophages)argon a base of disorders caused bytheinherited deficiency of lysosomal enzymes multiform inthemetabolism of glycosaminogly prat( halter),resulting inthewidespread intracellular and extracellular accumulation ofGAG.TypeGene subscript enzymeGAG depositedIInheritancepatternHurler syndrome (mononuclear phagocyte system I-H)IDUA (4p16.3)Alpha-L-iduronidaseDermatan convert, 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, soft (MPS II-B)IDS(Xq28)IduronatesulfataseDermatan sulfate, heparan sulfateXRSanfilippo syndrome A (MPS II I-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 cod totheaccumulation ofGAG. Hypertelorism has been account in MPS fictitious charactersIII,II andVII. Pseudoproptosis due to shallow orbit has been describe in a patie nt with MPS VIand MPS II.2. CorneaThe extracellular matrix of corneal stroma contains dermatan sulfate and keratan sulfate in equal proportion. some(prenominal) dermatan sulfate and keratan sulfate are combined 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(ip)(ip) 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 inthemean fibril diameter of collagen andanincrease in fib ril spacingarenoted in the corneal stroma of patients with MPS I. These structural alterations in collagen fibrils may contribute to light scattering. But the corneal clouding is mainly due totheaccumulation of GAGs in all the layers of cornea with increase 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 lessening 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 onerousness is variable, and it may be increased or normal.Corneal hysteresis is increased. Cornealedemaoccurs in cases withincreased intra-ocularpressure(IOP).3.Optic spunkGAGsare the major components oftheextracellular matrix oftheoptic boldness designate.Proteoglycan s containing chondritin sulfate and dermatan sulfate are located in lamina cribrosa, supporting tissues of the optic nerve head worry 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 canalthatleadsto discoedema(pseudopapilloedema). It can also be due to raised intracranial pressure manifesting as true papilloedema.Long-standing axonal compression or papilloedemacan lead to junior-grade optic atrophy.Theaccumulation of GAG in ganglion cells of retina can lead to axonal degeneration and optic atrophy.Optic nerve involvement is more unremarkably 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 segment structures can lead tothenarrowing of cant over resulting in acute incline arrest and chronic angle closure glaucoma. Anterior segmentoptical coherence tomography(OCT)imaging in mucopolysacchridosis suggests crowded anterior segment and increased corneal burdensomeness in type VI thanintype I.Theaccumulation of GAG in trabecular cells can lead to features similar 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 progress ion and severity of glaucomatous optic neuropathy may be compromised by corneal clouding and discoedema. Anterior segment OCT is a valuable tool intheassessment of angle, particularly in patients with corneal clouding. Ocular responseanalysercan be usedfor the immaculate 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 abstracted 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. sclerotic coatScleral thickening may lead totheuveal effusion syndrome.Suggested Reading1.Villas-Boas FS, Fernandes Filho DJ, Acosta AX.Ocular findings in patients with mucopolysaccharidosis.Arq Bras Ofta lmol201174(6)430434.2.Viestenz A, Shin YS, Viestenz A, Naumann GO.Ocularmanifestation ofmucopolysaccharidosis I-S (Scheiessyndrome).Klin Monbl Augenheilkd2002219(10)745748.