• Users Online: 277
  • Print this page
  • Email this page


 
 Table of Contents  
REVIEW ARTICLE
Year : 2022  |  Volume : 2  |  Issue : 1  |  Page : 5-10

Clinical review on mucopolysaccharidosis and its ocular significance


Department of Ophthalmology, IGMC and RI, Puducherry, India

Date of Submission14-Aug-2022
Date of Decision22-Aug-2022
Date of Acceptance23-Aug-2022
Date of Web Publication05-Oct-2022

Correspondence Address:
Dr. A Mary Stephen
Department of Ophthalmology, IGMC and RI, Puducherry
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jocr.jocr_12_22

Rights and Permissions
  Abstract 


A condition with deficiency of various enzymes which plays a crucial role in the degradation of glycosaminoglycans (GAG) is termed to be mucopolysaccharidosis (MPS). The disease entity is due to abnormal breakdown and diffuse accumulation of GAG in the various system including brain, eye, muscle, lungs, heart, and gastrointestinal system. The disease spectrum is highly varied from slight phenotypic changes to severe life-threatening illness. Morbidity, especially low visual acuity is due to the involvement of cornea (clouding of the cornea), optic nerve abnormality, and also retinopathy. Marked impairment of physical and intellectual function is common. The diagnosis is mostly clinical and advanced testing including enzyme assay and gene testing is required for typing and pinpoint diagnosis. The treatment options are limited in most cases as enzyme replacement therapy is not widely available and expensive. Bone marrow transplantation has been found to be successful but still a cumbersome option. Visual morbidity can be reduced by performing keratoplasty if corneal clouding is significant and visual prognosis is often guarded.

Keywords: Bone marrow transplantation, cornea clouding, enzyme replacement therapy, glycosaminoglycans, keratoplasty, mucopolysaccharidosis


How to cite this article:
Jayasri P, Stephen A M. Clinical review on mucopolysaccharidosis and its ocular significance. J Ophthalmol Clin Res 2022;2:5-10

How to cite this URL:
Jayasri P, Stephen A M. Clinical review on mucopolysaccharidosis and its ocular significance. J Ophthalmol Clin Res [serial online] 2022 [cited 2023 Oct 4];2:5-10. Available from: http://www.jocr.in/text.asp?2022/2/1/5/357888




  Introduction Top


Mucopolysaccharidosis (MPS) is a heterogeneous group of disorders due to defective lysosomal enzymes resulting in abnormal degradation of glycosaminogycans and so its accumulation in the cellular level results in multi-organ dysfunction. Till date, seven types with 13 subgroups have been identified for MPS. Most types are autosomal recessive in nature except Hunter syndrome which is X-linked. The clinical features often overlap between various types and enzyme assay can give final confirmatory diagnosis.


  Types Top


The exact distribution of MPS syndrome has not been ascertained and MPS Type I especially Hurler syndrome (IH) has increased prevalence and distribution.

MPS Type I occurs due to the deficiency of alpha-l-iduronidase enzyme, IDUA gene on the short arm of chromosome 4. Type I MPS has three phenotypic subdivisions called IH, Scheie syndrome (IS),  Hurler-Scheie syndrome More Details (IHS). There will be abnormal accumulation of heparan sulfate and dermatan sulfate.

  • IH is more severe with onset around 1–2 years of age and often patient expires in the first decade if treatment is not initiated[1]
  • IHS is comparatively less severe type with an onset around three to 7 years of life and has a longer lifespan
  • IS has the same features as IHS but a slightly late age of onset.


All three subdivisions of MPS Type I will have ocular manifestations.

Hunter syndrome is Type II MPS that occurs as a result of iduronate-2-sulfatase deficiency (chromosome Xq28). The onset is often at birth and presentation is usually by 2–4 years. Heparan sulfate and dermatan sufate accumulate in excess and progresses through the first decade.[2] The cornea remains unaffected but posterior segment manifestations are more pronounced. Mortality is commonly observed by the second decade with exceptions to mild cases where life expectancy is near the normal range.

Sanfilippo syndrome (Type III MPS) occurs due to a deficiency of multiple enzymes:

  • anfillipo A, III A. Heparan-N-Sulphatase deficiency
  • Sanfillipo B, III B. Alpha-N-Acetylglicosaminidase deficiency
  • Sanfillipo C, III C. Alpha-glucosaminide acetyltransferase deficiency
  • Sanfillipo D, III D. N-acetylglucosamine-6-sulphatase deficiency.


All the above types are characterized by the accumulation of heparan sulfate with onset between 2 and 6 years of age. III A and III B MPS is associated with SGSH gene mutation (chromosome 17q) and NAGLU gene. Neurocognitive symptoms predominate with features such as delayed speech, gait abnormality, hyperactivity, and pyramidal signs. Mortality by the third decade in most cases.[3],[4]>

Morquio syndrome (Type IV MPS) has two types:

  • Morquio A, IV A. N-acetylgalactosamine-6-sulphatase deficiency with the accumulation of keratan sulfate, chondroitin-6-sulphate
  • Morquio B, IV B. Beta-galactosidase deficiency with the accumulation of keratin sulfate.


In Type IV MPS, the onset of the disease is by 1st year of life with serious skeletal abnormalities. There will be respiratory abnormalities and spinal anomalies often by the late second late of life and the quality of life will be poor as most patients will be wheelchair-bound. Mutations of the genes GALNS (chromosome 16) and GLB1 (chromosome 3) are associated with MPS IV.

Maroteaux Lamy (Type VI MPS) is due to the deficiency of N-acetylgalactosamine-4-sulphatase resulting in the accumulation of dermatan sulfate and chondroitin-4-sulfate. The involved gene is ARSB on chromosome 5.[1] Onset is by 2 years of age with progressive growth retardation and mortality is a result of cardiopulmonary complications.

Sly syndrome (Type VII MPS) occurs due to the deficiency of beta-glucuronidase resulting in the accumulation of chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, and heparan sulfate. Mutation in the gene GUSB (chromosome 7) leads to the enzyme deficiency. The clinical spectrum of the disease is highly variable and not well understood as the disease's entity is very rare.[1]

Natowicz syndrome (Type IX MPS) is the rarest which is characterized by the accumulation of hyaluronan due to hyaluronidase enzyme efficiency. The disease is poorly understood and progressive craniofacial/skeletal abnormalities have been found.[1]


  Clinical Features Top


The incidence rate varies markedly depending on the type of MPS, and overall, it is approximately one in 25,000 livebirths.[5] The age of presentation and severity varies as per the phenotype. Ocular and systemic features often overlap between the different types of MPS; however, glaucoma, corneal clouding can present by the first decade and optic neuropathy by the second decade.[6]

Ocular features

Progressive corneal clouding is the most common ocular presentation and glycosaminoglycans (GAG) tend to deposit in all the layers of the cornea and result in disruption of the collagen fiber alignment leading to opacification and thickening.[7] [Figure 1] Elevated intraocular pressure (IOP) occurs due to the accumulation of GAGs in the trabecular meshwork which can lead to open-angle as well as closed-angle glaucoma. Proptosis and hypertelorism are seen in few cases which can cause keratoconjunctivtis sicca and corneal irregularities. Other uncommon ocular findings include hypermetropia and astigmatism due to abnormal GAG deposition in the cornea and sclera. Abnormal deposition in extraocular muscles results in strabismus, intracranial complications will manifest as disc edema. Pigmentary retinopathy has been the manifestation in certain MPS variants.[8]
Figure 1: Slit lamp photography of patient showing diffuse corneal clouding with sparing of the central visual axis in MPS-I. MPS: Mucopolysaccharidosis

Click here to view


Glaucoma is one of the common manifestations of MPS variants Hurler, Morquio and Maroteaux Lamy syndromes. Overall, the prevalence of glaucoma in MPS patients varies from 2.1% to 12.5%.[9] Around 10% cases of MPS I will have associated glaucoma. A case series by Ashworth et al. gives the details about the evaluation and prevalence of glaucoma in various MPS syndromes and reported the highest prevalence among MPS I (9.2%), MPS II (7.1%) and MPS IV A and MPS VI.[10] Open-angle glaucoma has been hypothesized to occur as a result of abnormal limbal and trabecular meshwork thickening.[11] Angle-closure glaucoma occurs due to swelling of cells in Schlemm's canal, abnormal intracellular cyst, and vesicles formation along the ciliary body and iris.[12],[13]>

The systemic manifestation of MPS is varied and the same has been explained briefly in [Table 1].
Table 1: Systemic manifestations of various mucopolysaccharidosis syndromes

Click here to view



  Tools for Evaluation Top


Most cases of MPS will have overlapping ocular features and poor cooperation of patients due to mental subnormality makes the clinical evaluation difficult. Corneal clouding, glaucoma, retinopathy, and optic nerve dysfunction were common manifestations; hazy media due to corneal deposition often restricts posterior segment evaluation.[14]

Multiple ocular investigative modalities are available for detailed assessment in these patients and the same has been described briefly [Table 2].
Table 2: Examination and investigations of the eye in mucopolysaccharidosis

Click here to view


Tonometry

The IOP assessment in most cases may not be reliable due to the accumulation of GAG within the cells of corneal stroma which in turn will affect the normal corneal rigidity resulting in falsely elevated values by applanation tonometry.[7] Type I and VI MPS has a significant association between corneal clouding and IOP. Out of various IOP measuring techniques, central corneal thickness-corrected Goldmann Applanation Tonometry reading gives more reliable value.[10]

Objective corneal clouding assessment

Most cases of MPS will have some corneal changes and few may not be clinically evident. Subjective staging of the disease is based on clinical parameters such as extent of corneal clouding and visibility of iris/anterior segment structures.[15],[16]>

Densitometry software in Scheimpflug-based devices and iris recognition cameras will give a better idea about the corneal clouding in MPS.[17],[18]>

Anterior segment optical coherence tomography

It provides details about corneal thickness and level of involvement from epithelium to the endothelium. Detailed morphology of the anterior segment and angle will be provided by anterior segment optical coherence tomography (AS-OCT). A study done by Zhang et al. using swept-source AS-OCT showed narrow angles in the majority of patients with MPS I.[19]

Ultrasound biomicroscopy

This modality also gives detailed anterior segment evaluation such as AS-OCT, but it is a contact procedure. Both tools are helpful in the preoperative planning of patients with glaucoma and corneal opacity.[20]

Confocal microscopy

In MPS, GAGs will be deposited in all the layers of the cornea which was also confirmed by histochemical studies. In vivo confocal microscopy has been used to observe and report the presence of cytoplasmic vacuoles by Stewart et al.[21]
Figure 2: Clinical image of the patient with MPS showing coarse facies with frontal bossing and sparse scalp hairs. MPS: Mucopolysaccharidosis

Click here to view


  • MPS I-S: Bright cells in the basal epithelium with round or elliptical mid-stromal keratocytes. Hyperreflective round bodies are seen in the anterior descemet layer[22]
  • MPS IV: Normal epithelium and endothelium. Diffuse, irregular hyperreflectivity noted in stroma with granular appearance of keratocyte cytoplasm[21]
  • MPS VI: Irregular shaped keratocytes with hyporeflective regions in the stroma.[23]


Reports from Stewart et al., Grupcheva et al., and Patel et al.[21],[22],[23] have described the corneal features using In vivo confocal microscopy, but the predictive value of confocal data in differentiating MPS variants has not been described.

Ultrasound B-scan

Posterior segment evaluation can be done in cases with severe corneal clouding. Scleral thickening and development of uveal effusion are observed in patients with MPS II.[24]

Electroretinography

Reduced b-wave on dark adaptation indicates rod-cone degeneration. Retinopathy has been observed in MPS I, II, and III.[25]

Visual-evoked potentials will help to identify patients with optic nerve dysfunction.


  Treatment of mucopolysaccharidosis Top


Treatment of MPS involves a multidisciplinary approach that involves the pediatricians, cardiologists, endocrinologists, ophthalmologists, and most importantly the patient's family members. There are various treatment options available that should be tailored according to the patient's needs.

Systemic manifestations can be treated by:

  • Enzyme replacement therapy (ERT)
  • Hematopoietic stem cell transplantation.


Ocular treatment for corneal clouding:

  • Symptomatic-Photochromatic glasses
  • Penetrating keratoplasty
  • Deep anterior lamellar keratoplasty (DALK).


Future treatment options:

  • Targeted gene therapy
  • Substrate deprivation therapy.
Figure 3: Radiograph images of MPS patients with prominent elongated skull bones with bossing (a) typical orb ribs commonly seen in Morquio syndrome (b) short stubby metacarpals and metatarsals (c and d) with the incomplete fusion of bones. MPS: Mucopolysaccharidosis

Click here to view



  Enzyme Replacement Therapy Top


ERT helps in the degradation of GAG that is accumulated in the lysosomes. It acts in the visceral organs and decreases the number of stored GAG.[26] This helps in the reduction of hepatomegaly. The rate of growth in height and weight and the range of movement of limbs are found to increase significantly after ERT.[27] Transient hypersensitivity reactions during infusions have been reported. ERT does not halt the disease progression in the eye and brain due to the presence of blood-retinal barrier and blood − brain barrier. Hence, it has no role in preventing visual deterioration.[28] The treatment had a varied effect on corneal clouding with reported stabilization and even worsening.[29]


  Hematopoietic Stem Cell Transplantation Top


Hematopoietic stem cell transplant is beneficial if started before 2 years of age. It has shown to reduce urinary GAG and decreases organomegaly effectively.[30],[31],[32],[33],[34] Some authors reported a deterioration of cognitive function despite successful HSCT.[35],[36],[37],[38] Others observed stabilization or even improvement of the course of disease compared to untreated siblings.[39],[40],[41],[42] HSCT does not prevent or halt the progression of corneal involvement. In a study conducted by Guffon et al.[43] involving 25 patients with MPS I, who were treated with HSCT, 50% of patients eventually required corneal transplantation due to the progression of corneal clouding. Teär Fahnehjelm et al.[44] in a study on eight patients with MPS I reported that corneal clouding increased during the follow-up period after initiating HSCT in 5 out of 8 patients.


  Substrate Deprivation Therapy Top


This newer modality is still being evaluated and it acts by reducing the production of GAG chains which are the natural substrates. This reduction will balance the reduced enzyme level and so balance the turnover of GAG. They are chemical inhibitors that can reach various sites as they can cross blood − brain and cornea easily. GAG nonspecific inhibitor Rhodamine-B has impact on normal and MPS-affected cells.[45] Another compound under evaluation is Genistein which inhibits GAG production in various MPS types especially I, II, and III by acting through an epidermal growth factor-dependent pathway.[46],[47]>


  Gene Therapy Top


This treatment modality is aimed to arrest or reverse the disease entity. Miyadera et al. investigated about adeno-associated virus IDUA gene addition technique for alpha-L-iduronidase deficiency.[48] Animal studies have shown intrastromal and intracameral injection resulted in a reduction in corneal clouding[48],[49]> Study by Kamata et al. showed successful treatment of corneal clouding in mice with MPS VII with the administration of human beta-glucuronidase expressed by adenovirus.[50]


  Penetrating Keratoplasty and Deep Anterior Lamellar Keratoplasty Top


The definitive treatment modality to improve visual acuity in patients with corneal clouding as a result of MPS in corneal transplantation. Preoperative assessment must include other causes of vision loss and carefully assess the visual benefit before surgery. Co-existing pathologies, especially blepharitis, corneal vascularization should be addressed prior and possibility of opacification of graft and graft rejection/failure should always be explained in detail. A multicentre trial has shown graft survival in 94% of postkeratoplasty patients with significant visual improvement in over 60% of them.[51] Naumann and Rummelt had observed clearing of host cornea around the transplanted tissue in MPS and attributed due to enzyme diffusion from the donor to host cornea.[52] A clinical review has shown better visual outcome following penetrating keratoplasty in corneal clouding with MPS and reported stable visual acuity with better graft survival on follow-up for over a decade.[53] A large multicenter trial found graft rejection in 23% of cases postpenetrating keratoplasty, but the final visual outcome was good with graft survival in 94% of cases.[51]

The deposition of GAG occurs in the corneal stroma in MPS and endothelium is affected in very severe disease and so DALK is another viable option for visual rehabilitation. However, the conventional technique for DALK like the big bubble method will be difficult due to abnormal deposition of GAG in the corneal stroma. A retrospective review found DALK provides a better outcome in the absence of significant scarring and graft survival is around 90% with good visual recovery in MPS with corneal clouding.[54] Devices such as AS-OCT and ultrasound biomicroscopy help to assess the stromal involvement. Studies have shown the conventional technique of DALK is useful in MPS patients and significant visual recovery noted with a very low risk for rejection/failure.[54],[55]>

Conclusion: MPS is a multisystem disorder that requires multidisciplinary approach for its evaluation and management. Ocular involvement is varied and corneal clouding is common with glaucoma, retinopathy being other visually disturbing associations. Treatment modalities in many cases are not very reachable and the outcomes of it are still experimental. Corneal clouding can be treated with a good success rate by penetrating keratoplasty/DALK.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ganesh A, Bruwer Z, Al-Thihli K. An update on ocular involvement in mucopolysaccharidoses. Curr Opin Ophthalmol 2013;24:379-88.  Back to cited text no. 1
    
2.
Wraith JE. Enzyme replacement therapy in mucopolysaccharidosis type I: Progress and emerging difficulties. J Inherit Metab Dis 2001;24:245-50.  Back to cited text no. 2
    
3.
Yogalingam G, Hopwood JJ. Molecular genetics of mucopolysaccharidosis type IIIA and IIIB: Diagnostic, clinical, and biological implications. Hum Mutat 2001;18:264-81.  Back to cited text no. 3
    
4.
Ozkinay F, Emecen DA, Kose M, Isik E, Bozaci AE, Canda E, et al. Clinical and genetic features of 13 patients with mucopolysaccarhidosis type IIIB: Description of two novel NAGLU gene mutations. Mol Genet Metab Rep 2021;27:100732.  Back to cited text no. 4
    
5.
Tomatsu S, Pitz S, Hampel U. Ophthalmological findings in mucopolysaccharidoses. J Clin Med 2019;8:1467.  Back to cited text no. 5
    
6.
Martin R, Beck M, Eng C, Giugliani R, Harmatz P, Muñoz V, et al. Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome). Pediatrics 2008;121:e377-86.  Back to cited text no. 6
    
7.
Ashworth JL, Biswas S, Wraith E, Lloyd IC. Mucopolysaccharidoses and the eye. Surv Ophthalmol 2006;51:1-17.  Back to cited text no. 7
    
8.
Fahnehjelm KT, Törnquist AL, Winiarski J. Ocular axial length and corneal refraction in children with mucopolysaccharidosis (MPS I-Hurler). Acta Ophthalmol 2012;90:287-90.  Back to cited text no. 8
    
9.
Kong W, Zhang J, Lu C, Ding Y, Meng Y. Glaucoma in mucopolysaccharidoses. Orphanet J Rare Dis 2021;16:312.  Back to cited text no. 9
    
10.
Ashworth J, Flaherty M, Pitz S, Ramlee A. Assessment and diagnosis of suspected glaucoma in patients with mucopolysaccharidosis. Acta Ophthalmol 2015;93:e111-7.  Back to cited text no. 10
    
11.
Ferrari S, Ponzin D, Ashworth JL, Fahnehjelm KT, Summers CG, Harmatz PR, et al. Diagnosis and management of ophthalmological features in patients with mucopolysaccharidosis. Br J Ophthalmol 2011;95:613-9.  Back to cited text no. 11
    
12.
Spellacy E, Bankes JL, Crow J, Dourmashkin R, Shah D, Watts RW. Glaucoma in a case of Hurler disease. Br J Ophthalmol 1980;64:773-8.  Back to cited text no. 12
    
13.
Nowaczyk MJ, Clarke JT, Morin JD. Glaucoma as an early complication of Hurler's disease. Arch Dis Child 1988;63:1091-3.  Back to cited text no. 13
    
14.
Del Longo A, Piozzi E, Schweizer F. Ocular features in mucopolysaccharidosis: Diagnosis and treatment. Ital J Pediatr 2018;44:125.  Back to cited text no. 14
    
15.
Fahnehjelm KT, Ashworth JL, Pitz S, Olsson M, Törnquist AL, Lindahl P, et al. Clinical guidelines for diagnosing and managing ocular manifestations in children with mucopolysaccharidosis. Acta Ophthalmol 2012;90:595-602.  Back to cited text no. 15
    
16.
Couprie J, Denis P, Guffon N, Reynes N, Masset H, Beby F. Ocular manifestations in patients affected by Morquio syndrome (MPS IV). J Fr Ophtalmol 2010;33:617-22.  Back to cited text no. 16
    
17.
Elflein HM, Hofherr T, Berisha-Ramadani F, Weyer V, Lampe C, Beck M, et al. Measuring corneal clouding in patients suffering from mucopolysaccharidosis with the Pentacam densitometry programme. Br J Ophthalmol 2013;97:829-33.  Back to cited text no. 17
    
18.
Aslam TM, Shakir S, Wong J, Au L, Ashworth J. Use of iris recognition camera technology for the quantification of corneal opacification in mucopolysaccharidoses. Br J Ophthalmol 2012;96:1466-8.  Back to cited text no. 18
    
19.
Zhang JR, Wang JH, Lin HZ, Lee YC. Anterior chamber angles in different types of mucopolysaccharidoses. Am J Ophthalmol 2020;212:175-84.  Back to cited text no. 19
    
20.
Dada T, Aggarwal A, Vanathi M, Gadia R, Panda A, Gupta V, et al. Ultrasound biomicroscopy in opaque grafts with post-penetrating keratoplasty glaucoma. Cornea 2008;27:402-5.  Back to cited text no. 20
    
21.
Stewart S, McGhee CN, Patel DV. In vivo confocal microscopy of the cornea in Morquio syndrome. Eye (Lond) 2012;26:1394-5.  Back to cited text no. 21
    
22.
Grupcheva CN, Craig JP, McGhee CN. In vivo microstructural analysis of the cornea in Scheie's syndrome. Cornea 2003;22:76-9.  Back to cited text no. 22
    
23.
Patel DV, Ku JY, Kent-Smith B, McGhee CN. In vivo microstructural analysis of the cornea in Maroteaux-Lamy syndrome. Cornea 2005;24:623-5.  Back to cited text no. 23
    
24.
Vine AK. Uveal effusion in Hunter's syndrome. Evidence that abnormal sclera is responsible for the uveal effusion syndrome. Retina 1986;6:57-60.  Back to cited text no. 24
    
25.
Caruso RC, Kaiser-Kupfer MI, Muenzer J, Ludwig IH, Zasloff MA, Mercer PA. Electroretinographic findings in the mucopolysaccharidoses. Ophthalmology 1986;93:1612-6.  Back to cited text no. 25
    
26.
Gaffke L, Pierzynowska K, Podlacha M, Brokowska J, Węgrzyn G. Changes in cellular processes occurring in mucopolysaccharidoses as underestimated pathomechanisms of these diseases. Cell Biol Int 2021;45:498-506.  Back to cited text no. 26
    
27.
Kakkis ED, Muenzer J, Tiller GE, Waber L, Belmont J, Passage M, et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med 2001;344:182-8.  Back to cited text no. 27
    
28.
Pitz S, Ogun O, Bajbouj M, Arash L, Schulze-Frenking G, Beck M. Ocular changes in patients with mucopolysaccharidosis I receiving enzyme replacement therapy: A 4-year experience. Arch Ophthalmol 2007;125:1353-6.  Back to cited text no. 28
    
29.
Pitz S, Ogun O, Arash L, Miebach E, Beck M. Does enzyme replacement therapy influence the ocular changes in type VI mucopolysaccharidosis? Graefes Arch Clin Exp Ophthalmol 2009;247:975-80.  Back to cited text no. 29
    
30.
Aldenhoven M, Wynn RF, Orchard PJ, O'Meara A, Veys P, Fischer A, et al. Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: An international multicenter study. Blood 2015;125:2164-72.  Back to cited text no. 30
    
31.
Poe MD, Chagnon SL, Escolar ML. Early treatment is associated with improved cognition in Hurler syndrome. Ann Neurol 2014;76:747-53.  Back to cited text no. 31
    
32.
Muenzer J. Early initiation of enzyme replacement therapy for the mucopolysaccharidoses. Mol Genet Metab 2014;111:63-72.  Back to cited text no. 32
    
33.
Laraway S, Breen C, Mercer J, Jones S, Wraith JE. Does early use of enzyme replacement therapy alter the natural history of mucopolysaccharidosis I? Experience in three siblings. Mol Genet Metab 2013;109:315-6.  Back to cited text no. 33
    
34.
Clarke LA, Wraith JE, Beck M, Kolodny EH, Pastores GM, Muenzer J, et al. Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I. Pediatrics 2009;123:229-40.  Back to cited text no. 34
    
35.
Hoogerbrugge PM, Brouwer OF, Bordigoni P, Ringden O, Kapaun P, Ortega JJ, et al. Allogeneic bone marrow transplantation for lysosomal storage diseases. The European Group for Bone Marrow Transplantation. Lancet 1995;345:1398-402.  Back to cited text no. 35
    
36.
Shapiro EG, Lockman LA, Balthazor M, Krivit W. Neuropsychological outcomes of several storage diseases with and without bone marrow transplantation. J Inherit Metab Dis 1995;18:413-29.  Back to cited text no. 36
    
37.
Klein K, Krivit W, Whitley CB, Cool V, Fuhrmann M, De Alarcon P, et al. Cognitive outcome of eleven children with Sanfilippo syndrome after bone marrow transplantation and successful engraftment. Bone Marrow Transplant 1995;15:S176-81.  Back to cited text no. 37
    
38.
Sivakumur P, Wraith JE. Bone marrow transplantation in mucopolysaccharidosis type IIIA: A comparison of an early treated patient with his untreated sibling. J Inherit Metab Dis 1999;22:849-50.  Back to cited text no. 38
    
39.
Hobbs JR. Displacement bone marrow transplantation for some inborn errors. J Inherit Metab Dis 1990;13:572-96.  Back to cited text no. 39
    
40.
Vellodi A, Young E, New M, Pot-Mees C, Hugh-Jones K. Bone marrow transplantation for Sanfilippo disease type B. J Inherit Metab Dis 1992;15:911-8.  Back to cited text no. 40
    
41.
Kurtzberg J, Szabolcs P, Wood S, Ciocci T, Prasad VK, Parikh SH, et al. Treatment of pediatric patients with Sanfilippo syndrome (MPS IIIA and IIIB) with unrelated umbilical cord blood transplantation. Biol Blood Marrow Transplant 2005;11:83-4.  Back to cited text no. 41
    
42.
Prasad VK, Mendizabal A, Parikh SH, Szabolcs P, Driscoll TA, Page K, et al. Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: Influence of cellular composition of the graft on transplantation outcomes. Blood 2008;112:2979-89.  Back to cited text no. 42
    
43.
Guffon N, Pettazzoni M, Pangaud N, Garin C, Lina-Granade G, Plault C, et al. Long term disease burden post-transplantation: Three decades of observations in 25 Hurler patients successfully treated with hematopoietic stem cell transplantation (HSCT). Orphanet J Rare Dis 2021;16:60.  Back to cited text no. 43
    
44.
Teär Fahnehjelm K, Olsson M, Chen E, Hengstler J, Naess K, Winiarski J. Children with mucopolysaccharidosis risk progressive visual dysfunction despite haematopoietic stem cell transplants. Acta Paediatr 2018;107:1995-2003.  Back to cited text no. 44
    
45.
Roberts AL, Thomas BJ, Wilkinson AS, Fletcher JM, Byers S. Inhibition of glycosaminoglycan synthesis using rhodamine B in a mouse model of mucopolysaccharidosis type IIIA. Pediatr Res 2006;60:309-14.  Back to cited text no. 45
    
46.
Jakóbkiewicz-Banecka J, Piotrowska E, Narajczyk M, Barańska S, Wegrzyn G. Genistein-mediated inhibition of glycosaminoglycan synthesis, which corrects storage in cells of patients suffering from mucopolysaccharidoses, acts by influencing an epidermal growth factor-dependent pathway. J Biomed Sci 2009;16:26.  Back to cited text no. 46
    
47.
Kloska A, Jakóbkiewicz-Banecka J, Narajczyk M, Banecka-Majkutewicz Z, Węgrzyn G. Effects of flavonoids on glycosaminoglycan synthesis: Implications for substrate reduction therapy in Sanfilippo disease and other mucopolysaccharidoses. Metab Brain Dis 2011;26:1-8.  Back to cited text no. 47
    
48.
Miyadera K, Conatser L, Llanga TA, Carlin K, O'Donnell P, Bagel J, et al. Intrastromal gene therapy prevents and reverses advanced corneal clouding in a canine model of mucopolysaccharidosis I. Mol Ther 2020;28:1455-63.  Back to cited text no. 48
    
49.
Vance M, Llanga T, Bennett W, Woodard K, Murlidharan G, Chungfat N, et al. AAV gene therapy for MPS1-associated corneal blindness. Sci Rep 2016;6:22131.  Back to cited text no. 49
    
50.
Kamata Y, Okuyama T, Kosuga M, O'hira A, Kanaji A, Sasaki K, et al. Adenovirus-mediated gene therapy for corneal clouding in mice with mucopolysaccharidosis type VII. Mol Ther 2001;4:307-12.  Back to cited text no. 50
    
51.
Ohden KL, Pitz S, Ashworth J, Magalhães A, Marinho DR, Lindahl P, et al. Outcomes of keratoplasty in the mucopolysaccharidoses: An international perspective. Br J Ophthalmol 2017;101:909-12.  Back to cited text no. 51
    
52.
Naumann GO, Rummelt V. Clearing of the para-transplant host cornea after perforating keratoplasty in Maroteaux-Lamy syndrome (type VI-A mucopolysaccharidosis). Klin Monbl Augenheilkd 1993;203:351-60.  Back to cited text no. 52
    
53.
Bothun ED, Decanini A, Summers CG, Orchard PJ, Tolar J. Outcome of penetrating keratoplasty for mucopolysaccharidoses. Arch Ophthalmol 2011;129:138-44.  Back to cited text no. 53
    
54.
Harding SA, Nischal KK, Upponi-Patil A, Fowler DJ. Indications and outcomes of deep anterior lamellar keratoplasty in children. Ophthalmology 2010;117:2191-5.  Back to cited text no. 54
    
55.
da Silva Ricardo JR, Medhi J, Pineda R. Indications for and outcomes of deep anterior lamellar keratoplasty in mucopolysaccharidoses. J Pediatr Ophthalmol Strabismus 2013;50:376-81.  Back to cited text no. 55
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Types
Clinical Features
Tools for Evaluation
Treatment of muc...
Enzyme Replaceme...
Hematopoietic St...
Substrate Depriv...
Gene Therapy
Penetrating Kera...
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed2715    
    Printed284    
    Emailed0    
    PDF Downloaded165    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]