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Mucopolysaccharidosis Type I - Treatment & Management

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Overview

Management of the multiple organ system involvement in MPS I requires a multi-specialty and multi-disciplinary approach, ideally guided by the Medical Home, that will be detailed below. Two relatively new treatment interventions are available to decrease the impact of the metabolic abnormalities patients with MPS I:
  • Successful hematopoietic stem cell transplantation (HSCT) increases survival, reduces facial coarseness and hepatosplenomegaly, improves hearing, and preserves normal heart function, however cardiac valvular disease, skeletal manifestations and corneal clouding may continue to progress. If HSCT is accomplished before evidence of significant developmental delay (usually under 2 years), the degree and rate of cognitive decline will likely be reduced.
  • Enzyme replacement therapy can significantly reduce liver size, increase height and weight, decrease joint restriction, lessen sleep apnea, and improve breathing in individuals with intermediate MPS I. The benefit of ERT in those with severe disease has not been assessed, however one patient with severe MPS, who had been treated for 3 years with ERT, continued to experience decline in respiratory status, musculoskeletal and spinal involvement, and developmental skills. [Thomas: 2006] Because the recombinant enzyme is not thought to cross the blood-brain barrier, the best option to reduce the risk of cognitive impairment remains early HSCT.
  • Combined ERT and HSCT is another option for individuals with severe MPS I. Providing ERT before and into the peri-HSCT period may improve the child's existing respiratory and cardiac manifestations to a certain extent which may reduce the risk of transplant-related complications. [Tolar: 2008]
  • Intrathecal ERT, injecting the enzyme into the spinal fluid, is a therapy currently under investigation for the treatment of cognitive decline in severe MPS I.

Primary Care Roles

The medical home can serve as a liaison between the patient, family, and multiple subspecialists that the patient will encounter, which will increase the quality and access to care. The medical home can also facilitate early diagnosis and discuss potential therapeutic and treatment options for MPS I in a time-sensitive manner. Coordination of selected therapies (i.e., stem-cell transplant for those with severe MPS I) should be initiated by the medical home and involve the patient, subspecialists, and the specialty institution that will perform the procedures. The medical home should also establish a relationship with the pharmaceutical company that supplies the recombinant enzyme and a home health care nursing team for those patients who elect to have enzyme replacement therapy (ERT). Periodic assessments of the progression of the condition (i.e., cardiovascular, skeletal, developmental outcomes) both pre-treatment and during treatment is essential and can be performed in conjunction with the patient's primary care provider and subspecialists.

The primary care physician (PCP) may be the first one to suspect this disorder and to approach the family about testing to confirm the diagnosis and the level of severity. Since individuals with MPS I can have involvement of almost every organ system, a multi-disciplinary approach to management is required. Families, with the counsel and guidance of their PCP, must weigh the benefits and risks related to enzyme replacement therapy, hematopoietic stem cell transplants, and the many surgical interventions that may be recommended.

Pearls And Alerts

Dysostosis multiplex can lead to instability of the spine, including the atlantoaxial joint. Careful positioning and avoidance of hyperextension of the neck are necessary.

Induction of anesthesia can be difficult; smaller-than-anticipated endotracheal tubes are usually required for intubation because the trachea may be narrowed and the vocal cords thickened.

Recovery from anesthesia may be slow and postoperative airway obstruction is a common problem.

Practice Guidelines

Muenzer J, Wraith JE, Clarke LA.
Mucopolysaccharidosis I: management and treatment guidelines.
Pediatrics. 2009;123(1):19-29. PubMed abstract

Systems

Cardiology

Cardiac involvement includes cardiomyopathy, endocardiofibroelastosis, progressive valvular disease, and coronary artery disease. Aortic valvular disease and occasional poly-valvular disease is common in the attenuated forms of MPS I. Echocardiograms and ECGs are necessary to monitor valvular involvement and cardiac function. Cardiac valve replacement may be required. Sudden death from arrhythmia and cardiovascular collapse may occur. It is very difficult to assess coronary artery disease because it is a generalized phenomenon instead of focal occlusion.

Subspecialist Collaborations and Other Resources

Pediatric Cardiology (see Services below for relevant providers)

Essential to involve pediatric cardiology for evaluation and ongoing management of cardiac complications.

Musculoskeletal

Orthopedic problems will exist, to some degree, for all MPS I patients. Because of the risk for spinal compression, parents/patients should be instructed to avoid "high risk" activities, such as contact sports, and should be cautioned about manipulation of the cervical spine. Range of motion exercises appear to offer some benefits in preserving joint function and should be started early. Hip replacement, knee surgery, Achilles tendon release are a few of the more common surgical procedures that may improve function and quality of life.

Subspecialist Collaborations and Other Resources

Pediatric Orthopedics (see Services below for relevant providers)

Collaborating with pediatric orthopedists comfortable with the management of MPSI is very important.

Respiratory

Restrictive lung disease is common in MPS I, and pulmonary function testing usually demonstrates diminished lung volumes. Respiratory infections often lead to secondary bacterial infections of the sinuses or ears, requiring antibiotic treatment. Some patients will need chronic antibiotic therapy and many patients become allergic to antibiotics and some acquire resistant infections. Instruct parents to avoid over-the-counter drugs commonly used to treat colds and congestion (antihistamines that make mucus thicker and harder, decongestants that contain stimulants which raise blood pressure and narrow blood vessels, cough suppressants that may contribute to sleep apnea).

Subspecialist Collaborations and Other Resources

Pediatric Pulmonology (see Services below for relevant providers)

Airway obstruction and sleep apnea is common. Enlarged tonsils and adenoids may need to be removed. Supplemental oxygen and/or a tracheostomy is sometimes necessary for patients with chronic dyspnea. For sleep apnea, CPAP or BiPAP are non-invasive options if the patient can adjust to wearing the mask and mouthpiece at night. Complications include the build-up of mucus in the nasal passages or discomfort if the pressure is inappropriately high. A sleep study and consultation with a pulmonologist is recommended before placing the patient on a positive airway pressure device. Pulmonary function testing with lung vital capacity measurements are helpful in monitoring cardio-respiratory status and response to therapies.

Neurology

Communicating hydrocephalus can be present without overt ventriculomegaly, is often underdiagnosed, and may be associated with some cortical atrophy. The greater the neurologic involvement, the greater the risk for developing hydrocephalus. Annual brain imaging (CT or MRI) may allow presymptomatic identification of hydrocephalus. If there is a rapid increase in head circumference, a lumbar puncture with measurement of opening pressure of cerebrospinal fluid (CSF) is the preferred method for assessing the degree of pressure elevation.

Prior to surgery, the cervical region should be evaluated to determine if there is evidence of obstruction at the foramen magnum placing the spinal cord at risk. A laminectomy may need to be performed at the time of surgery. Specialists recommend a high-pressure shunt (10-15 mm Hg) to prevent rapid decompression.

Subspecialist Collaborations and Other Resources

Pediatric Neurology (see Services below for relevant providers)

Pediatric neurologists may be helpful in evaluating, monitoring and managing neurologic complications such as hydrocephalus and carpal tunnel syndrome.

Pediatric Neurosurgery (see Services below for relevant providers)

Pediatric neurosurgeons will provide initial and ongoing evaluation of children with hydrocephalus, as well as place the appropriate shunt and manage potential complications.

Ears/Hearing

Hearing loss, both conductive and sensorineural, is common and is correlated with the severity of somatic manifestations of disease. The most important contributing factors include: frequent middle ear infections caused by storage of GAGs within the oro-pharynx, dysostosis of the ossicles of the middle ear, scarring of the tympanic membrane, and damage to the eighth nerve. [Kakkis: 2001] In most cases, hearing loss is sensorineural and can be managed by use of a hearing aid.

Otitis media is a persistent problem in children with MPS1. Pneumococcal vaccine may be helpful. Pseudomonas aeruginosa and staphyloccus aureus are more common as children age. Corticosteroids may also be helpful. Some children may benefit from eliminating common food allergens (soy, citrus, peanuts, wheat, fish, eggs, corn and tomatoes) from their diet.

Subspecialist Collaborations and Other Resources

Audiology (see Services below for relevant providers)

Refer patients for routine testing and consider early intervention with hearing aids, which are generally underutilized in MPS patients.

Pediatric Otolaryngology (see Services below for relevant providers)

Comanagement of children with recurrent/persistent otitis media and/or hearing loss with an ENT specialist is recommended. With draining ears, fungal infection should be considered. Tympanostomy tubes with heavy-duty grommets is recommended, along with removal of the adenoids and tonsils, is often necessary to prevent recurrent/persistent infection.

Eyes/Vision

Visual deficits occur, especially in dim light, if corneal clouding is severe. Some patients cannot tolerate bright lights (sunglasses and visors can help). Night blindness can increase fear of walking anywhere when it is dark. Patients may suffer from glaucoma, severe visual impairment with retinal degeneration, optic nerve compression and atrophy, and the loss of peripheral vision. Corneal transplantation is not routinely offered in individuals with severe MPS I, but may prove beneficial in those with the attenuated forms, though there is the risk that the donor cornea would accumulate material.

Subspecialist Collaborations and Other Resources

Pediatric Ophthalmology (see Services below for relevant providers)

Referral is indicated for initial and periodic evaluation and management of visual acuity, corneal opacity, optic nerve abnormalities, and peripheral vision.

Gastro-Intestinal & Bowel Function

Inability to maintain adequate nutrition may call for supplementation, but the decision to change to enteral nutrition is a difficult one. In assessing the need for enteral nutrition, monitor the child's weight, caloric intake, choking/gagging problems, episodes of pneumonia, and time required for feeding.

Diarrhea, possibly due to a defect in the autonomic nervous system, is common in younger patients. Try decreasing roughage in the diet and, if taking antibiotics, adding a live-culture yogurt or probiotics to the diet. Constipation can be a problem in older patients, requiring laxatives or enemas.

Subspecialist Collaborations and Other Resources

Pediatric Gastroenterology (see Services below for relevant providers)

May be helpful in managing difficult nutritional challenges, as well as hard-to-manage constipation.

Dental

Dental caries and abscessed teeth occur easily because the teeth are poorly formed, with fragile enamel causing them to be susceptible to infection and decay. Instruct parents to clean the teeth gently and to avoid foods that contribute to dental decay. If the water is not treated with fluoride, prescribe daily fluoride tablets or drops. Prophylactic antibiotics are advised before and after dental treatment if the child has any cardiac involvement. Gum cysts are common and can be treated by simple excision.

Subspecialist Collaborations and Other Resources

General Dentistry for CSHCN (see Services below for relevant providers)

Routine dental care with a dentist familiar and comfortable with children with challenging medical problems can make a huge difference in their oral health.

Development (general)

Early development in children with severe MPS I may be normal; however, developmental delays and progressive mental retardation ensue secondary to build-up of glycosaminoglycans within the brain. Children with severe MPS I may plateau and subsequently regress in their developmental skills. In individuals with attenuated MPS I, intellect may be normal or nearly normal.

Subspecialist Collaborations and Other Resources

Developmental Pediatrics (see Services below for relevant providers)

Refer to a developmental specialist for testing and early intervention. The family may need assistance in developing plans for school (IEP and 504).

Resources

Information & Support

For Professionals

Mucopolysaccharidosis Type I (GeneReviews)
An excellent review of MPS I includes genetics, clinical description, management, resources and references from the GeneReviews Web site funded by the National Institutes of Health.

Hurler syndrome (OMIM)
A very detailed description of Hurler syndrome, its genetics, clinical features, diagnosis, and treatment; from Online Mendelian Inheritance in Man (OMIM), from the National Center for Biotechnology Information.

For Parents and Patients

Support

National MPS Society
Provides information about the disorder, research, support for families, fund raising, and efforts to increase public awareness about MPS and related disorders. Allows users to contact and communicate directly with other parents/patients.

Hide & Seek Foundation
"Hide & Seek is a community of people dedicated to finding treatments and cures for a devastating genetic condition called Lysosomal Disease."

LysoLife Community
"The LysoLife Community connects families, friends and caregivers for support and inspiration. The LysoLife Community is sponsored by the Hide & Seek Foundation in partnership with Inspire."

Mucopolysaccharidosis syndromes resources (KUMC)
A list of international resources for patients/families; from the University of Kansas Medical Center, Medical Genetics - Genetics and Rare Conditions Site.

General

Mucopolysaccharidosis Type I (Genetics Home Reference)
Excellent overview of MPS I for families/patients, from Genetics Home Reference, a service of the National Library of Medicine. Includes links for more consumer-level information and support.

Mucopolysaccharidoses Fact Sheet
The National Institute of Neurological Disorders and Strokes (NINDS) provides a fact sheet addresing signs and symptoms, risks, types, treatments, research and resources.

Hurler syndrome (MedlinePlus Encyclopedia)
Brief overview and links, from the National Library of Medicine and National Institutes of Health.

Practice Guidelines

Muenzer J, Wraith JE, Clarke LA.
Mucopolysaccharidosis I: management and treatment guidelines.
Pediatrics. 2009;123(1):19-29. PubMed abstract

Patient Education

National MPS Society Booklets
More than 10 booklets (large files) about mucopolysaccharidoses and related diseases for patients, families, and providers; includes information about MPS I, II, III, IV, VI, VII; ML II/III; daily living; anesthesia; resources, and more.

National MPS Society Fact Sheets
More than 25 fact sheets about mucopolysaccharidoses and related diseases for patients, families, and providers; topics include cardiac problems, caregiver support, family coping strategies, melatonin, transplants, pamidronate, tube feedings, stem cell transplants, and more.

Tools

Aldurazyme (Laronidase) Information for Physicians (PDF Document 247 KB)
Two page handout for physicians covering pharmacology, dosage, precautions, and contraindications.

Services

Audiology

See all Audiology services providers (56) in our database.

Developmental Pediatrics

See all Developmental Pediatrics services providers (2) in our database.

General Dentistry for CSHCN

See all General Dentistry for CSHCN services providers (121) in our database.

Pediatric Cardiology

See all Pediatric Cardiology services providers (2) in our database.

Pediatric Gastroenterology

See all Pediatric Gastroenterology services providers (2) in our database.

Pediatric Neurology

See all Pediatric Neurology services providers (3) in our database.

Pediatric Neurosurgery

See all Pediatric Neurosurgery services providers (1) in our database.

Pediatric Ophthalmology

See all Pediatric Ophthalmology services providers (5) in our database.

Pediatric Orthopedics

See all Pediatric Orthopedics services providers (2) in our database.

Pediatric Otolaryngology

See all Pediatric Otolaryngology services providers (9) in our database.

Pediatric Pulmonology

See all Pediatric Pulmonology services providers (5) in our database.

For other services related to this condition, browse our Services categories or search our database.

Studies

Current studies of MPS I (ClinicalTrials.gov)
A list of ongoing clinical studies for which patients may be eligible. The list includes registered studies that are closed and may have links to their published outcomes.

MPS I Registry
An ongoing, observational database that tracks natural history and outcomes of patients with MPS I. The Registry was initiated worldwide in April 2003 as an international observational program sponsored by BioMarin/Genzyme LLC and administered by Genzyme Corporation. Registration is voluntary, free, and confidential.

Helpful Articles

The articles listed below the PubMed search summarize stem cell/bone marrow therapy and enzyme replacement therapy as treatments for MPS I.

PubMed search on Mucopolysaccharidosis Type I

Muenzer J, Fisher A.
Advances in the treatment of mucopolysaccharidosis type I.
N Engl J Med. 2004;350(19):1932-4. PubMed abstract

Wraith JE.
The first 5 years of clinical experience with laronidase enzyme replacement therapy for mucopolysaccharidosis I.
Expert Opin Pharmacother. 2005;6(3):489-506. PubMed abstract

Wraith JE, Clarke LA, Beck M, Kolodny EH, Pastores GM, Muenzer J, Rapoport DM, Berger KI, Swiedler SJ, Kakkis ED, Braakman T, Chadbourne E, Walton-Bowen K, Cox GF.
Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase).
J Pediatr. 2004;144(5):581-8. PubMed abstract

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;24(1):97-101. PubMed abstract

Souillet G, Guffon N, Maire I, Pujol M, Taylor P, Sevin F, Bleyzac N, Mulier C, Durin A, Kebaili K, Galambrun C, Bertrand Y, Froissart R, Dorche C, Gebuhrer L, Garin C, Berard J, Guibaud P.
Outcome of 27 patients with Hurler's syndrome transplanted from either related or unrelated haematopoietic stem cell sources.
Bone Marrow Transplant. 2003;31(12):1105-17. PubMed abstract

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;32(2):213-5. PubMed abstract

Grewal SS, Wynn R, Abdenur JE, Burton BK, Gharib M, Haase C, Hayashi RJ, Shenoy S, Sillence D, Tiller GE, Dudek ME, van Royen-Kerkhof A, Wraith JE, Woodard P, Young GA, Wulffraat N, Whitley CB, Peters C.
Safety and efficacy of enzyme replacement therapy in combination with hematopoietic stem cell transplantation in Hurler syndrome.
Genet Med. 2005;7(2):143-6. PubMed abstract

Staba SL, Escolar ML, Poe M, Kim Y, Martin PL, Szabolcs P, Allison-Thacker J, Wood S, Wenger DA, Rubinstein P, Hopwood JJ, Krivit W, Kurtzberg J.
Cord-blood transplants from unrelated donors in patients with Hurler's syndrome.
N Engl J Med. 2004;350(19):1960-9. PubMed abstract
Review of bone marrow transplant as a treatment option in individuals with Hurler syndrome.

Authors

Author: Pilar L. Magoulas MS, CGC, 2/2009
Content Last Updated: 6/2009

Page Bibliography

Kakkis ED, Muenzer J, Tiller GE, Waber L, Belmont J, Passage M, Izykowski B, Phillips J, Doroshow R, Walot I, Hoft R, Neufeld EF.
Enzyme-replacement therapy in mucopolysaccharidosis I.
N Engl J Med. 2001;344(3):182-8. PubMed abstract

Thomas JA, Jacobs S, Kierstein J, Van Hove J.
Outcome after three years of laronidase enzyme replacement therapy in a patient with Hurler syndrome.
J Inherit Metab Dis. 2006;29(6):762. PubMed abstract

Tolar J, Grewal SS, Bjoraker KJ, Whitley CB, Shapiro EG, Charnas L, Orchard PJ.
Combination of enzyme replacement and hematopoietic stem cell transplantation as therapy for Hurler syndrome.
Bone Marrow Transplant. 2008;41(6):531-5. PubMed abstract / Full Text
Hurler syndrome (mucopolysaccharidosis type I, MPS IH) is characterized by a deficiency of alpha-L-iduronidase resulting in progressive multiorgan dysfunction. Study results suggest treatment of MPS IH patients with combination of ERT and HSCT therapy to further investigate its potential to enhance outcomes with HSCT.