Mucopolysaccharidoses Types I-VII Treatment & Management
- Author: Janette Baloghova, MD, PhD; Chief Editor: Dirk M Elston, MD more...
No cure exists for mucopolysaccharidosis; current treatment is symptomatic and supportive. However, possible treatments are being investigated in several clinical trials.
In patients with mucopolysaccharidosis type I, treatment with recombinant human alpha-L-iduronidase reduces lysosomal storage in the liver and ameliorates some clinical manifestations of the disease.
In patients with mucopolysaccharidosis type I, laronidase significantly improves respiratory function and physical capacity, reduces GAG storage, and has a favorable safety profile.
A Hurler syndrome fibroblast cell line heterozygous for the IDUA gene that encodes alpha-L-iduronidase stop mutations Q70X or W402X shows a significant increase in alpha-L-iduronidase activity when cultured in the presence of gentamicin, resulting in the restoration of 2.8% of the normal alpha-L-iduronidase activity.
Allogeneic bone marrow transplantation (BMT) is the only long-lasting treatment that ameliorates or halts the aggressive course of the disease. Pulmonary hemorrhage is an unusual complication of BMT.
Allogeneic hematopoietic SCT, used in severe forms of the disease, markedly prolongs survival, alleviates ventricular hypertrophy, and preserves cardiac function, but cardiac valves continue to thicken and valvular insufficiency progresses.
Cell therapy with human amniotic epithelial cells was developed as an alternative method for enzyme replacement therapy in congenital lysosomal storage disorders, but only limited therapeutic efficacy has been reported. Some studies suggest that the transplantation of human amniotic epithelial cells transduced with adenoviral vectors can be used for the treatment of congenital lysosomal storage disorders. The multiple positive effects include reconstruction of the CNS.
Neonatal screening of these diseases should be mandatory to vastly improve outcomes. Plans are being implemented to use dried blood spots on filter paper, as is commonly performed for many other genetic diseases. Many new therapies are being adopted, which should enhance positivity and acceptance of treatment by hematopoietic SCT.
Many children who undergo SCT have deterioration in hearing following SCT. A high-risk group of children can be delineated who may benefit from more intensive audiologic monitoring following SCT.
For Maroteaux-Lamy syndrome, BMT is the only definitive form of enzyme replacement therapy available. Umbilical cord blood transplantation has also been reported as a treatment of this syndrome.
Yasuda et al report a case report with long-term observation after hematopoietic stem cells transplantation (HSCT) in a patient with mucopolysaccharidosis type I (Hurler syndrome). HSCT at an early stage of mucopolysaccharidosis type I (Hurler syndrome) provides a marked positive impact on clinical central nervous system and skeletal manifestations, bone pathology, and GAG levels. Thus, HSCT should be a primary standard care of mucopolysaccharidosis type I (Hurler syndrome) at an early stage.
Therapy with glucocorticoids, high doses of vitamin A, thyroid hormone, lidase, and growth hormone has been attempted. Glucocorticoids and a corticotropin have been used to block the synthesis of acid mucopolysaccharides. High doses of vitamin A have been used in an effort to increase the urinary excretion of mucopolysaccharides; however, the amount excreted and the clinical response have varied. Lidase is a hyaluronidase that digests mucopolysaccharides. Thyroid hormone substitution is used in patients with hypothyroidism. Some patients with mucopolysaccharidosis are shown to have growth hormone deficiency, and in these cases, growth hormone therapy may be beneficial. Symptomatic anticonvulsive therapy is indicated when epilepsy is present. The prognosis is better and therapy is more successful when treatment is started early.
Treatment with recombinant human N -acetylgalactosamine 4-sulfatase (rhASB) is another possibility in mucopolysaccharidosis type VI. rhASB treatment reportedly was well-tolerated, and reduced lysosomal storage is evidenced by a dose-dependent reduction in urinary GAG.
Flavonoids, as compounds related to genistein (an inhibitor of glycosaminoglycans [GAG] synthesis), are natural candidates for drugs that could be used to manage the neurological symptoms of mucopolysaccharidosis.
Kloska et al have tested the effects of 4 different flavonoids in assays for GAG synthesis, lysosomal structures, and phosphorylation of epidermal growth factor receptor. Skin fibroblasts obtained from mucopolysaccharidosis type IIIA and mucopolysaccharidosis type IIIB patients were used in all experiments, and a human dermal fibroblasts adult cell line was used as a healthy control line. Their studies revealed that apigenin (a flavone), daidzein (an isoflavone), kaempferol (a flavonol), and naringenin (a flavanone) caused a decrease in the efficiency of GAG synthesis, although only daidzein and kaempferol caused statistically significant differences relative to untreated cells. Nevertheless, in the presence of all these compounds, lysosomal storage in mucopolysaccharidosis type IIIA fibroblasts was significantly decreased. Flavonoids can be considered as potential drugs. Obviously, further tests, including those with animal models, are necessary to prove their safety for organisms.
Treatments in clinical trials
No cure exists for mucopolysaccharidosis; treatment is symptomatic and supportive. However, possible treatments are being investigated in several clinical trials.
Mucopolysaccharidosis type I
Laronidase (Aldurazyme) is an enzyme replacement therapy for patients with mucopolysaccharidosis type I, a progressive, debilitating, and fatal genetic disease for which specific drug treatments currently are available. In a press release in September 2002, BioMarin and Genzyme included clinical data from the 6-month, placebo-controlled, phase 3 trial of laronidase; 6 months of data from the ongoing open-label, phase 3 extension study; and 3 years of data from the phase 1 trial and extension study. Laronidase was approved in the United States in April 2003.
The study of a double-blinded, placebo-controlled trial reported by Muenzer et al supports the use of weekly infusions of idursulfase in the treatment of mucopolysaccharidosis type II. Idursulfase was generally well tolerated, but infusion reactions did occur. Idursulfase antibodies were detected in 46.9% of patients.[54, 55]
Mucopolysaccharidosis type II
In a press release from October 2002, Transkaryotic Therapies Inc (TKT) reported results from a phase 1/2 study evaluating its investigational enzyme replacement therapy with I2S as a treatment of Hunter syndrome. The randomized, double-blinded, placebo-controlled study evaluated the safety of I2S (human I2S produced by genetic engineering technology) and its clinical activity in 12 patients with Hunter syndrome. Three doses were studied (0.15 mg/kg, 0.5 mg/kg, and 1.5 mg/kg), and within each dose group, 3 patients were randomized to receive I2S and 1 was to receive placebo by a 60-min intravenous infusion biweekly for 6 months.
In the trial, I2S administration was generally well tolerated, and in the phase 1/2 trials, evidence of clinical activity with Hunter syndrome, including reduced cardiac mass, stabilized pulmonary function, and reduced GAG levels, was demonstrated. The most common adverse effects from I2S treatment were hives, chills, fever, and facial flushing. Only 1 of the 9 patients who were treated developed antibody to I2S.
Mucopolysaccharidosis type IVA
Elosulfase alfa (Vimizim; BioMarin Pharmaceutical, Inc.) was approved by the FDA in February 2014 for patients with Morquio A syndrome (mucopolysaccharidosis Type IVA [MPS IVA]). Approval was supported by a 24-week, randomized, clinical trial involving 176 patients. The primary endpoint of the trial, change in 6-minute walk distance at 24 weeks, was statistically significant in patients who received weekly elosulfase alfa 2 mg/kg IV infusions. The walking distance improved in the elosulfase alfa group with a mean increase of 22.5 meters over placebo. Walking ability was sustained in patients who continued weekly elosulfase alfa for an additional 48 weeks.
Mucopolysaccharidosis type VI
The clinical trial of rhASB (Aryplase), an investigational enzyme replacement therapy for mucopolysaccharidosis type VI, continues to evaluate the efficacy, safety, and pharmacokinetics of weekly intravenous infusions of 1 mg/kg of rhASB in 10 patients with mucopolysaccharidosis type VI. In June 2002, BioMarin Pharmaceutical announced findings from the 24-week open-label extension of the phase 1 clinical trial; the enzyme was well tolerated by all patients, and reduced urinary excretion of GAG was maintained in both treatment arms.
It was confirmed in the phase 3 of the randomized, double-blinded, placebo-controlled, multicenter, multinational study that rhASB significantly improves endurance, reduces urinary GAG excretion, and has an acceptable safety profile. After 24 weeks, patients receiving rhASB walked on average 92 meter more in the 12-minute walk test and climbed 5.7 stairs per minute more in a 3-minute stair climb test than patients receiving placebo. Urinary GAG declined by -227 ±18 mcg/mg more with rhASB than placebo. Patients exposed to the drug experienced positive clinical benefits despite the presence of antibody to the protein.
Mucopolysaccharidosis type VII
Emil Kakkis, MD, PhD, and William Sly, MD, have received a grant to develop enzyme replacement for mucopolysaccharidosis type VII. They are making steady progress with BioMarin Pharmaceutical, but no timeline for human clinical trials is projected.
Updated clinical trial data and recruiting
For updated clinical trial results and for trials that are completed and recruiting see ClinicalTrials.gov.
Treatment is symptomatic. Orthopedic surgeries may be required for mucopolysaccharidosis types I, II, IV, VI, and VII to correct the deformities and increase patient quality of life. Tonsillectomy and adenoidectomy may help improve the patients’ respiratory status. Other complications can be managed with myringotomy, heart-valve replacement, and decompression of the cervical spinal cord.
Surgical procedures may include corneal transplantation and correction of nerve entrapments in the hands.
Correction of the contractures and osteal deformities may be performed. For patients with mucopolysaccharidosis type IV, cervical myelopathy should be prevented by surgery of the cervical spine.
Occipital to C3 decompression and fusion with autogenous rib grafts may be performed. The youngest patient who underwent this successful posterior cervical arthrodesis was 17-month-old boy with Sly syndrome.
Genetic counseling is of great importance to ensure prenatal diagnosis.
Mucopolysaccharidoses create a special challenge for the otolaryngologist. With the rare types of mucopolysaccharidosis type IV and mucopolysaccharidosis type I-S, a skilled practitioner is required to manage airway complications. The erratic deposits of mucopolysaccharides throughout the trachea should be taken into account when a decision is made to stent the airway. Proper management requires an airway that is custom made to meet the patient's needs.
Mucopolysaccharidosis type I (Hurler syndrome)
Complications include heart valve damage from thickening due to coronary artery disease, severe mental retardation, umbilical and inguinal hernia, deafness, premature death, and constipation alternating with diarrhea.
Mucopolysaccharidosis type II (Hunter syndrome)
Complications include airway obstruction in the late-onset form, progressive mental deterioration in the early-onset form (severe form), progressive loss of ability to perform daily living activities in the early-onset form (severe form), progressive hearing loss in both the mild and severe forms, progressive joint stiffness leading to contractures of the joints in the early-onset form (severe form), and carpal tunnel syndrome. Of the complications observed after tracheotomy, infrastomal tracheal stenosis and stomal narrowing are frequent. Intubation in children with mucopolysaccharidosis type II is more difficult (20 times more) than in other children of a similar age or weight.
Mucopolysaccharidosis type III (Sanfilippo syndrome)
Complications include blindness, seizures, mental retardation, progressive neurologic disease leading to patients becoming wheelchair bound, and the inability to care for oneself.
Mucopolysaccharidosis type IV (Morquio syndrome)
Complications include heart failure, difficulty with vision, walking problems due to abnormal curvature of the spine, and breathing problems. Abnormal neck bones can cause spinal cord damage that can result in severe disease, including paralysis, if not noticed early. Spinal fusion can prevent this complication.
Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome)
Complications include hearing loss, vision loss, carpal tunnel syndrome, and valvular heart disease.
Genetic counseling may be performed.
Prenatal diagnosis is possible. Amniocentesis can be performed; cells in the amniotic fluid are cultured, and the alpha-L-iduronidase activity in the cells is determined.
As determined by Altarescu et al, preimplantation genetic diagnosis (PGD) is a reliable method to prevent pregnancies of children affected with Hunter syndrome. In addition, they report the first ever derivation of a Hunter syndrome (46,XX) human stem cell line from embryos carrying the iduronate-2-sulfatase and oculocutaneous albinism type 2 mutations. PGD is a technique that precludes the need for pregnancy termination in cases of an affected fetus, by virtue of analysis of the 6- to 8-cell stage embryos (obtained by in vitro fertilization) and transfer of only unaffected embryos.
All patients with mucopolysaccharidosis type I should receive a comprehensive baseline evaluation, including neurologic, ophthalmologic, auditory, cardiac, respiratory, gastrointestinal, and musculoskeletal assessments. Additionally, all patients should be monitored every 6-12 months with individualized specialty assessments, to monitor disease progression and effects of intervention. Patients are best treated by a multidisciplinary team. Treatments consist of palliative/supportive care, hematopoietic stem cell transplantation, and enzyme replacement therapy. The patient's age (>2 y or 2 y), predicted phenotype, and developmental quotient help define the risk-to-benefit profile for hematopoietic SCT transplantation (higher risk but can preserve CNS function) versus enzyme replacement therapy (low risk but cannot cross the blood-brain barrier).
International expert panels recommend the evaluation of ocular features at least every 12 months for patients with mucopolysaccharidosis type I and mucopolysaccharidosis type VI.
Hamano K, Hayashi M, Shioda K, Fukatsu R, Mizutani S. Mechanisms of neurodegeneration in mucopolysaccharidoses II and IIIB: analysis of human brain tissue. Acta Neuropathol. 2008 May. 115(5):547-59. [Medline].
Hrebicek M, Mrazova L, Seyrantepe V, et al. Mutations in TMEM76* cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome). Am J Hum Genet. 2006 Nov. 79(5):807-19. [Medline].
Donida B, Marchetti DP, Biancini GB, et al. Oxidative stress and inflammation in mucopolysaccharidosis type IVA patients treated with enzyme replacement therapy. Biochim Biophys Acta. 2015 May. 1852(5):1012-9. [Medline].
Murphy AM, Lambert D, Treacy EP, O'Meara A, Lynch SA. Incidence and prevalence of mucopolysaccharidosis type 1 in the Irish republic. Arch Dis Child. 2009 Jan. 94(1):52-4. [Medline].
Malm G, Lund AM, Mansson JE, Heiberg A. Mucopolysaccharidoses in the Scandinavian countries: incidence and prevalence. Acta Paediatr. 2008 Nov. 97(11):1577-81. [Medline].
Héron B, Mikaeloff Y, Froissart R, et al. Incidence and natural history of mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece. Am J Med Genet A. 2011 Jan. 155A(1):58-68. [Medline].
Keilmann A, Läßig AK, Pollak-Hainz A, Mann WJ, Beck M, Hainz M. Adenoids of patients with mucopolysaccharidoses demonstrate typical alterations. Int J Pediatr Otorhinolaryngol. 2015 Feb. 79:115-8. [Medline].
Nakarat T, Läßig AK, Lampe C, Keilmann A. Alterations in speech and voice in patients with mucopolysaccharidoses. Logoped Phoniatr Vocol. 2014 Apr. 39(1):30-7. [Medline].
Perenc L. Anthropometric characteristics of four Polish children with mucopolysaccharidosis. BMC Research Notes. 2013. 6:246. [Full Text].
Miller BS, Fung EB, Kaizer A, et al. Longitudinal changes in linear growth and BMI in the mucopolysaccharidoses. Molecular Genetics and Metabolism. 2016 Feb. 117(2):S80-S81. [Full Text].
Ashrafi MR, Shabanian R, Mohammadi M, Kavusi S. Extensive Mongolian spots: a clinical sign merits special attention. Pediatr Neurol. 2006 Feb. 34(2):143-5. [Medline].
Panteliadis CP, Karatza ED, Tzitiridou MK, Koliouskas DE, Spiroglou KS. Lissencephaly and mongolian spots in Hurler syndrome. Pediatr Neurol. 2003 Jul. 29(1):59-62. [Medline].
Nemes A, Timmermans RG, Wilson JH, et al. The mild form of mucopolysaccharidosis type I (Scheie syndrome) is associated with increased ascending aortic stiffness. Heart Vessels. 2008 Mar. 23(2):108-11. [Medline].
Demitsu T, Kakurai M, Okubo Y, et al. Skin eruption as the presenting sign of Hunter syndrome IIB. Clin Exp Dermatol. 1999 May. 24(3):179-82. [Medline].
Sapadin AN, Friedman IS. Extensive Mongolian spots associated with Hunter syndrome. J Am Acad Dermatol. 1998 Dec. 39(6):1013-5. [Medline].
Ochiai T, Suzuki Y, Kato T, et al. Natural history of extensive Mongolian spots in mucopolysaccharidosis type II (Hunter syndrome): a survey among 52 Japanese patients. J Eur Acad Dermatol Venereol. 2007 Sep. 21(8):1082-5. [Medline].
Schwartz I, Vedolin L, Jardim LB, et al. Brain magnetic resonance imaging and spectroscopic findings inmucopolysaccharidosis type II. Acta Paediatrica. 2007. 96:109-11.
Kwon JY, Ko K, Sohn YB, et al. High prevalence of carpal tunnel syndrome in children with mucopolysaccharidosis type II (Hunter syndrome). Am J Med Genet A. 2011 Jun. 155A(6):1329-35. [Medline].
Dodsworth Ch, Burton B K,. Increased incidence of neonatal respiratory distress in infants withmucopolysaccharidosis type II (MPS II, Hunter syndrome). Molecular Genetics and Metabolism. 2013. [Full Text].
Wijburg FA, Wegrzyn G, Burton BK, Tylki-Szymanska A. Mucopolysaccharidosis type III (Sanfilippo syndrome) and misdiagnosis of idiopathic developmental delay, attention deficit/hyperactivity disorder or autism spectrum disorder. Acta Paediatr. 2013 May. 102(5):462-70. [Medline]. [Full Text].
Meyer A, Kossow K, Gal A, et al. Scoring evaluation of the natural course of mucopolysaccharidosis type IIIA (Sanfilippo syndrome type A). Pediatrics. 2007 Nov. 120(5):e1255-61. [Medline].
Alpoz AR, Coker M, Celen E, et al. The oral manifestations of Maroteaux-Lamy syndrome (mucopolysaccharidosis VI): a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006 May. 101(5):632-7. [Medline].
Oudit GY, Butany J, Williams WG, Siu SC, Clarke JT, Iwanochko RM. Left ventricular aneurysm in a patient with mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome): clinical and pathological correlation. Cardiovasc Pathol. 2007 Jul-Aug. 16(4):237-40. [Medline].
Okamura K, Munkhbat B, Batchimeg B, Tamiya G, Hozumi Y, Suzuki T. Case of a Mongolian child with extensive Mongolian spots in mucopolysaccharidosis type VI: identification of a novel mutation in the arylsulfatase B gene. J Dermatol. 2013 Sep. 40(9):758-9. [Medline].
Ashrafi MR, Tavasoli A, Shiva S, Parvaneh N, Tamizifar B. Diffuse dermal melanocytosis in two patients with Sandhoff disease and mucopolysaccharidosis VI. Int J Dermatol. 2013 Oct 18. [Medline].
Dickerman RD, Colle KO, Bruno CA Jr, Schneider SJ. Craniovertebral instability with spinal cord compression in a 17-month-old boy with Sly syndrome (mucopolysaccharidosis type VII): a surgical dilemma. Spine. 2004 Mar 1. 29(5):E92-4. [Medline].
Venkat-Raman N, Sebire NJ, Murphy KW. Recurrent fetal hydrops due to mucopolysaccharidoses type VII. Fetal Diagn Ther. 2006. 21(3):250-4. [Medline].
Delbecque K, Gaillez S, Schaaps JP. Histopathological diagnosis of a type vii mucopolysaccharidosis after pregnancy termination. Fetal Pediatr Pathol. 2009. 28(1):1-8. [Medline].
Ashworth JL, Kruse FE, Bachmann B, et al. Ocular manifestations in the mucopolysaccharidoses – a review. Clin Exp Ophthalmol. 2010. 38:12–22.
Lin HY, Chuang CK, Chen MR, et al. Cardiac structure and function and effects of enzyme replacement therapy in patients with mucopolysaccharidoses I, II, IVA and VI. Mol Genet Metab. 2016 Apr. 117(4):431-7. [Medline].
Gniadek TJ, Singer N, Barker NJ, et el. Cardiovascular pathologies in mucopolysaccharidosis type VII (Sly Syndrome). Cardiovasc Pathol. 2015 Sept-Oct. 24(5):322-6. [Medline].
Leone A, Rigante D, Amato DZ, et al. Spinal involvement in mucopolysaccharidoses: a review. Childs Nerv Syst. 2015 Feb. 31(2):203-12. [Medline].
Gallegos-Arreola MP, Machorro-Lazo MV, Flores-Martinez SE, et al. Urinary glycosaminoglycan excretion in healthy subjects and in patients with mucopolysaccharidoses. Arch Med Res. 2000 Sep-Oct. 31(5):505-10. [Medline].
Dean CJ, Bockmann MR, Hopwood JJ, Brooks DA, Meikle PJ. Detection of mucopolysaccharidosis type II by measurement of iduronate-2-sulfatase in dried blood spots and plasma samples. Clin Chem. 2006 Apr. 52(4):643-9. [Medline].
Di Natale P, Villani GR, Parini R, et al. Molecular markers for the follow-up of enzyme-replacement therapy in mucopolysaccharidosis type VI disease. Biotechnol Appl Biochem. 2008 Mar. 49:219-23. [Medline].
Blanchard S, Sadilek M, Scott CR, Turecek F, Gelb MH. Tandem mass spectrometry for the direct assay of lysosomal enzymes in dried blood spots: application to screening newborns for mucopolysaccharidosis I. Clin Chem. 2008 Dec. 54(12):2067-70. [Medline].
Randall DR, Colobong KE, Hemmelgarn H, et al. Heparin cofactor II-thrombin complex: a biomarker of MPS disease. Mol Genet Metab. 2008 Aug. 94(4):456-61. [Medline].
Dung VC, Tomatsu S, Montaño AM, et al. Mucopolysaccharidosis IVA: correlation between genotype, phenotype and keratan sulfate levels. Mol Genet Metab. 2013 Sep-Oct. 110(1-2):129-38. [Medline]. [Full Text].
de Santana Sarmento DJ, de Carvalho SH, Melo SL, et al. Mucopolysaccharidosis: radiographic findings in a series of 16 cases. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015 Dec. 120(6):e240-6. [Medline].
Gabrielli O, Polonara G, Regnicolo L, et al. Correlation between cerebral MRI abnormalities and mental retardation in patients with mucopolysaccharidoses. Am J Med Genet A. 2004 Mar 15. 125A(3):224-31. [Medline].
Matheus MG, Castillo M, Smith JK, Armao D, Towle D, Muenzer J. Brain MRI findings in patients with mucopolysaccharidosis types I and II and mild clinical presentation. Neuroradiology. 2004 Aug. 46(8):666-72. [Medline].
Husain AM, Escolar ML, Kurtzberg J. Neurophysiologic assessment of mucopolysaccharidosis III. Clin Neurophysiol. 2006 Sep. 117(9):2059-63. [Medline].
Cimaz R, Vijay S, Haase C, et al. Attenuated type I mucopolysaccharidosis in the differential diagnosis of juvenile idiopathic arthritis: a series of 13 patients with Scheie syndrome. Clin Exp Rheumatol. 2006 Mar-Apr. 24(2):196-202. [Medline].
Anawis MA. Hunter syndrome (MPS II-B): a report of bilateral vitreous floaters and maculopathy. Ophthalmic Genet. 2006 Jun. 27(2):71-2. [Medline].
Braunlin EA, Berry JM, Whitley CB. Cardiac findings after enzyme replacement therapy for mucopolysaccharidosis type I. Am J Cardiol. 2006 Aug 1. 98(3):416-8. [Medline].
Gassas A, Sung L, Doyle JJ, Clarke JT, Saunders EF. Life-threatening pulmonary hemorrhages post bone marrow transplantation in Hurler syndrome. Report of three cases and review of the literature. Bone Marrow Transplant. 2003 Jul. 32(2):213-5. [Medline].
Grewal SS, Krivit W, Defor TE, et al. Outcome of second hematopoietic cell transplantation in Hurler syndrome. Bone Marrow Transplant. 2002 Mar. 29(6):491-6. [Medline].
Yasuda E, Mackenzie W, Ruhnke K, et al. Long-term follow-up of post hematopoietic stem cell transplantation for Hurler syndrome: Clinical, biochemical, and pathological improvements. Mol Genet Metab Rep. 2015 Mar. 2:65-76. [Medline].
Harmatz P, Whitley CB, Waber L, et al. Enzyme replacement therapy in mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). J Pediatr. 2004 May. 144(5):574-80. [Medline].
Kloska A, Jakóbkiewicz-Banecka J, Narajczyk M, Banecka-Majkutewicz Z, Wegrzyn G. Effects of flavonoids on glycosaminoglycan synthesis: implications for substrate reduction therapy in Sanfilippo disease and other mucopolysaccharidoses. Metab Brain Dis. 2011 Mar. 26(1):1-8. [Medline]. [Full Text].
Muenzer J, Wraith JE, Beck M, et al. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006 Aug. 8(8):465-73. [Medline].
Wraith JE, Clarke LA, Beck M, et al. Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J Pediatr. 2004 May. 144(5):581-8. [Medline].
Muenzer J, Wraith JE, Clarke LA. Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics. 2009 Jan. 123(1):19-29. [Medline].
A Double-Blind Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome). NCT01275066. ClinicalTrials.gov. Available at http://clinicaltrials.gov/ct2/show/study/NCT01275066. Accessed: February 20, 2014.
Harmatz P, Giugliani R, Schwartz I, et al. Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study. J Pediatr. 2006 Apr. 148(4):533-539. [Medline].
Noh H, Lee JI. Current and potential therapeutic strategies for mucopolysaccharidoses. J Clin Pharm Ther. 2014 jun. 39(3):215-24. [Medline].
Frawley D, Fuenzalida D, Donath S, Yaplito-Lee J, Peters H. A retrospective audit of anesthetic techniques and complications in children with mucopolysaccharidoses. Pediatric Anesthesia. 2012. 22:737– 744.
Altarescu G, Renbaum P, Eldar-Geva T, et al. Preventing mucopolysaccharidosis type II (Hunter syndrome): PGD and establishing a Hunter (46, XX) stem cell line. Prenat Diagn. 2011 Jun 27. [Medline].
Hein LK, Bawden M, Muller VJ, Sillence D, Hopwood JJ, Brooks DA. alpha-L-iduronidase premature stop codons and potential read-through in mucopolysaccharidosis type I patients. J Mol Biol. 2004 Apr 30. 338(3):453-62. [Medline].
Caillaud C, Poenaru L. Gene therapy in lysosomal diseases. Biomed Pharmacother. 2000 Oct. 54(10):505-12. [Medline].
Fu H, Samulski RJ, McCown TJ, Picornell YJ, Fletcher D, Muenzer J. Neurological correction of lysosomal storage in a mucopolysaccharidosis IIIB mouse model by adeno-associated virus-mediated gene delivery. Mol Ther. 2002 Jan. 5(1):42-9. [Medline].
Gosele S, Dithmar S, Holz FG, Volcker HE. [Late diagnosis of Morquio syndrome. Clinical histopathological findings in a rare mucopolysaccharidosis]. Klin Monatsbl Augenheilkd. 2000 Aug. 217(2):114-7. [Medline].
Ito K, Ochiai T, Suzuki H, Chin M, Shichino H, Mugishima H. The effect of haematopoietic stem cell transplant on papules with 'pebbly' appearance in Hunter's syndrome. Br J Dermatol. 2004 Jul. 151(1):207-11. [Medline].
Jeong HS, Cho DY, Ahn KM, Jin DK. Complications of tracheotomy in patients with mucopolysaccharidoses type II (Hunter syndrome). Int J Pediatr Otorhinolaryngol. 2006 Oct. 70(10):1765-9. [Medline].
Kakavanos R, Turner CT, Hopwood JJ, Kakkis ED, Brooks DA. Immune tolerance after long-term enzyme-replacement therapy among patients who have mucopolysaccharidosis I. Lancet. 2003 May 10. 361(9369):1608-13. [Medline].
Kakkis ED, Muenzer J, Tiller GE, et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med. 2001 Jan 18. 344(3):182-8. [Medline].
Keeling KM, Brooks DA, Hopwood JJ, Li P, Thompson JN, Bedwell DM. Gentamicin-mediated suppression of Hurler syndrome stop mutations restores a low level of alpha-L-iduronidase activity and reduces lysosomal glycosaminoglycan accumulation. Hum Mol Genet. 2001 Feb 1. 10(3):291-9. [Medline].
Kim CH, Hwang HZ, Song SM, et al. Mutational spectrum of the iduronate 2 sulfatase gene in 25 unrelated Korean Hunter syndrome patients: identification of 13 novel mutations. Hum Mutat. 2003 Apr. 21(4):449-50. [Medline].
Krivit W. Allogeneic stem cell transplantation for the treatment of lysosomal and peroxisomal metabolic diseases. Springer Semin Immunopathol. 2004 Nov. 26(1-2):119-32. [Medline].
Lee V, Li CK, Shing MM, et al. Umbilical cord blood transplantation for Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI). Bone Marrow Transplant. 2000 Aug. 26(4):455-8. [Medline].
Leighton SE, Papsin B, Vellodi A, Dinwiddie R, Lane R. Disordered breathing during sleep in patients with mucopolysaccharidoses. Int J Pediatr Otorhinolaryngol. 2001 Apr 27. 58(2):127-38. [Medline].
Mahalingam K, Janani S, Priya S, Elango EM, Sundari RM. Diagnosis of mucopolysaccharidoses: how to avoid false positives and false negatives. Indian J Pediatr. 2004 Jan. 71(1):29-32. [Medline].
Mariotti P, Della Marca G, Iuvone L, et al. Sleep disorders in Sanfilippo syndrome: a polygraphic study. Clin Electroencephalogr. 2003 Jan. 34(1):18-22. [Medline].
Mok A, Cao H, Hegele RA. Genomic basis of mucopolysaccharidosis type IIID (MIM 252940) revealed by sequencing of GNS encoding N-acetylglucosamine-6-sulfatase. Genomics. 2003 Jan. 81(1):1-5. [Medline].
Nelson J, Crowhurst J, Carey B, Greed L. Incidence of the mucopolysaccharidoses in Western Australia. Am J Med Genet A. 2003 Dec 15. 123A(3):310-3. [Medline].
Prystowsky SD, Maumenee IH, Freeman RG, Herndon JH Jr, Harrod MJ. A cutaneous marker in the Hunter syndrome a report of four cases. Arch Dermatol. 1977 May. 113(5):602-5. [Medline].
Punnett A, Bliss B, Dupuis LL, Abdolell M, Doyle J, Sung L. Ototoxicity following pediatric hematopoietic stem cell transplantation: a prospective cohort study. Pediatr Blood Cancer. 2004 Jun. 42(7):598-603. [Medline].
Rigante D, Caradonna P. Secondary skeletal involvement in Sanfilippo syndrome. QJM. 2004 Apr. 97(4):205-9. [Medline].
Ross CJ, Bastedo L, Maier SA, Sands MS, Chang PL. Treatment of a lysosomal storage disease, mucopolysaccharidosis VII, with microencapsulated recombinant cells. Hum Gene Ther. 2000 Oct 10. 11(15):2117-27. [Medline].
Sands MS, Barker JE, Vogler C, et al. Treatment of murine mucopolysaccharidosis type VII by syngeneic bone marrow transplantation in neonates. Lab Invest. 1993 Jun. 68(6):676-86. [Medline].
Schiro JA, Mallory SB, Demmer L, Dowton SB, Luke MC. Grouped papules in Hurler-Scheie syndrome. J Am Acad Dermatol. 1996 Nov. 35(5 Pt 2):868-70. [Medline].
Scriver RC, Beaudet AL, Sly WS. The Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill; 1995.
Seyrantepe V, Tihy F, Pshezhetsky AV. The microcell-mediated transfer of human chromosome 8 restores the deficient N-acetylytransferase activity in skin fibroblasts of Mucopolysaccharidosis type IIIC patients. Hum Genet. 2006 Sep. 120(2):293-6. [Medline].
Shinhar SY, Zablocki H, Madgy DN. Airway management in mucopolysaccharide storage disorders. Arch Otolaryngol Head Neck Surg. 2004 Feb. 130(2):233-7. [Medline].
Weisstein JS, Delgado E, Steinbach LS, Hart K, Packman S. Musculoskeletal manifestations of Hurler syndrome: long-term follow-up after bone marrow transplantation. J Pediatr Orthop. 2004 Jan-Feb. 24(1):97-101. [Medline].
Whitley CB, Belani KG, Chang PN, et al. Long-term outcome of Hurler syndrome following bone marrow transplantation. Am J Med Genet. 1993 Apr 15. 46(2):209-18. [Medline].
Wolanczyk T, Banaszkiewicz A, Mierzewska H, Czartoryska B, Zdziennicka E. [Hyperactivity and behavioral disorders in Sanfilippo A (mucopolysaccharidosis type IIIA)--case report and review of the literature]. Psychiatr Pol. 2000 Sep-Oct. 34(5):831-7. [Medline].
|Mucopolysaccharidosis Type||Syndrome Name||Deficiency||EC Number|
|MPS type I-H||Hurler syndrome||Alpha-L-iduronidase||126.96.36.199|
|MPS type I-S
(formerly MPS type V)
|MPS type I-H/S||Hurler-Scheie syndrome||Alpha-L-iduronidase||N/A|
|MPS type II, mild||Hunter syndrome, mild form||L-sulfoiduronate sulfatase||N/A|
|MPS type II, severe||Hunter syndrome, severe form||L-sulfoiduronate sulfatase||188.8.131.52|
|MPS type III-A||Sanfilippo syndrome type A||Heparan sulfate sulfamidase||184.108.40.206|
|MPS type III-B||Sanfilippo syndrome type B||N -acetyl-alpha-D-glucosaminidase||220.127.116.11|
|MPS type III-C||Sanfilippo syndrome type C||Acetyl-coenzyme A (CoA): alpha-glucosamide N -acetyltransferase||18.104.22.168|
|MPS type III-D||Sanfilippo syndrome type D||N -acetyl-alpha-D-glucosamine-6-sulfatase||22.214.171.124|
|MPS type IV-A||Morquio syndrome, classic form||N -acetylgalactosamine-6-sulfatase (gal-6-sulfatase)||126.96.36.199|
|MPS type IV-B||Morquiolike syndrome||Beta-galactosidase||188.8.131.52|
|MPS type VI||Maroteaux-Lamy syndrome, mild form||N -acetylgalactosamine-4-sulfatase (arylsulfatase B)||N/A|
|MPS type VI||Maroteaux-Lamy syndrome, severe form||N -acetylgalactosamine-4-sulfatase (arylsulfatase B)||184.108.40.206|
|MPS type VII||Sly syndrome||Beta-glucuronidase||220.127.116.11|