AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Mucopolysaccharides consist of glycosaminoglycans attached to a link protein with a hyaluronic acid core. Lysosomal enzymes degrade these macromolecules into smaller components. Heparan sulfate, dermatan sulfate, and keratan sulfate are by-products of an incomplete degradation process. The accumulation of these compounds interferes with cell function.

Different forms of the disease were described separately throughout the 20th century. Their clinical presentations are varied depending on the type of enzyme defect and glycoprotein accumulated.

Related eMedicine topics:
Lysosomal Storage Disease
Madelung Deformity

Related Medscape topics:
Enzyme Replacement Effective in Patients With Hunter Syndrome
Enzyme Replacement Helpful in Mucopolysaccharidosis
Laronidase Prompts Improvement in Mucopolysaccharidosis

Pathophysiology

Defective activity of the lysosomal enzymes blocks the degradation process of mucopolysaccharides, leading to abnormal accumulation of heparan sulfate, dermatan sulfate, and keratan sulfate. These degradation by-products are then secreted and detected in the urine. Mucopolysaccharidosis (MPS) can be subclassified according to the type and amount of substance that accumulates, as follows: Hurler syndrome (MPS IH) (see Images 5, 7-8), Hurler-Scheie (MPS I-H/S), Scheie syndrome (MPS IS), Hunter syndrome (MPS II), Sanfilippo syndrome (MPS III), Morquio syndrome (MP IV) (see Images 1-4, 6), Maroteaux-Lamy syndrome (MPS VI), and Sly syndrome (MPS VII).^{1, 2, 3}

Frequency

International

The prevalence of all types of MPS is 1 case in 16,000-30,000 births. MPS III accounts for 80% of cases. These syndromes are found in persons of all ethnic groups, but prevalence is increased in Israeli Jews and French Canadians.

Mortality/Morbidity

These disease processes have significant effects on the growth and development of the musculoskeletal system, including joint stiffness or hyperlaxity, deformities, and progressive loss of function. Multiple other organ systems are involved. The type and extent of organ system involvement are variable depending on the subset of the disease. Most of these patients have shortened life spans and some of them die in infancy.

Race

These syndromes are found in all ethnic groups. Incidence of MPS II is increased in Israeli Jews, and incidence of MPS IV is increased in French Canadians.

Sex

All mucopolysaccharidoses are inherited as autosomal recessive disorders with the exception of Hunter syndrome (MPS II), which is inherited as sex-linked recessive condition. Thus, all patients with Hunter syndrome are males.

Age

Ages at which features of MPS present are somewhat variable. MPS features mostly present in the first few months of life. However, Morquio syndrome usually presents in children aged 2-4 years, and MPS IS and MPS VI can present late in childhood.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Patients with MPS have normal development initially. Abnormalities are seen in infancy or sometimes later in childhood. Multiple clinical features are seen in the patients in whom multiple organ systems are involved.

• CNS disease: Hydrocephalus is commonly seen in these patients. It is thought to be the result of a defect in cerebrospinal fluid reabsorption. The severity of hydrocephalus correlates with the severity of mental and neurologic retardation. Cervical spine myelopathy secondary to atlantoaxial instability is also commonly seen.
• Cardiovascular disease: Symptoms of heart disease are present in many patients with MPS. Many of them have angina-type symptoms secondary to arteriosclerosis and ischemia. They also can present with valvular dysfunction, hypertension, and congestive heart failure; sudden cardiovascular collapse and death are possible.
• Pulmonary disease: Obstructive airway disease is commonly seen in patients with MPS. It is caused by a narrowed trachea and bronchial airways, thickened vocal cords, and redundant tissue in the upper airway. These characteristics can cause problems ranging from sleep apnea to severe respiratory compromise and cor pulmonale.
• Ophthalmologic disease: Corneal clouding is seen in MPS and can cause significant loss of visual acuity. Glaucoma and chronic papilledema are common complications in several of the MPS conditions. Retinal degenerations are also seen and can be diagnosed with electroretinography.
• Hearing impairment: Deafness is reported in MPS and is thought to be of combined conductive and neurosensory origin. It is attributed to recurrent middle ear infections, deformity of the ossicles, and abnormalities of the inner ear.
• Musculoskeletal disease: Short stature is seen in all MPS conditions except MPS IS. Joint stiffness is a common feature in MPS with the exception MPS IV, in which joints demonstrate hyperlaxity. Other musculoskeletal presentations include symptoms of peripheral nerve entrapment, such as carpal tunnel syndrome, and tendon entrapment, such as trigger finger.^{4, 5}

Physical

• MPS IH (Hurler syndrome): Infants born with Hurler syndrome appear healthy at birth. Diagnosis is usually made in infants aged 6-24 months. Inguinal and umbilical hernias are commonly seen at birth. On physical examination, these patients are observed to have corneal clouding, hepatosplenomegaly, skeletal deformities (dysostosis multiplex), coarse facial features, large tongue, prominent forehead, joint stiffness, and short stature. They also have upper airway obstruction, recurrent ear infections, noisy breathing, and persistent nasal discharge. Other features include hirsutism, hearing loss, hydrocephalus, and mental retardation. Death usually occurs by age 10 years.^{4, 5, 6}
• MPS I-H/S (Hurler-Scheie syndrome): This is an intermediate form of Hurler syndrome with milder features. Onset is seen in children aged 3-8 years. These patients have normal intelligence and micrognathia, which gives them a characteristic facies. Corneal clouding, joint stiffness, and heart disease develop by the early to mid teens. Patients survive well into the third decade of life.
• MPS IS (Scheie syndrome): Onset occurs in patients older than 5 years. These patients have aortic valve disease, corneal clouding, and joint stiffness with broad short claw hands. They have normal intelligence and stature and a normal life span.
• MPS II (Hunter syndrome): Mild and severe forms exist, both of which have the same enzyme deficiency. This form of MPS is characterized by pebbly ivory skin lesions on the back, arms, and thighs. The extent of the skin lesions does not correlate with severity of the disease.^{7, 8}
• • MPS II, severe form: Onset of disease occurs in children aged 2-4 years, with severe progressive somatic and neurologic involvement. Coarse facial features, skeletal deformities (such as claw hand), and joint stiffness are present. These patients also have retinal degeneration with clear cornea and hydrocephalus, mental retardation, and aggressive behavior. Death occurs in patients aged 10-15 years.
  • MPS II, mild form: These patients have similar features to the severe form but a much slower rate of progression. They have normal intelligence and no hydrocephalus. Hearing impairment and loss of hand function secondary to joint stiffness and deformities are common in the mild form of Hunter. These patients survive into the sixth and seventh decades of life.
• MPS III (Sanfilippo syndrome): This appears to be the most common of the MPS disorders. Four subtypes of this disease exist, based on the lysosomal enzyme deficiency (types A, B, C, and D). However, these subtypes are not distinguishable clinically. Onset of the disease usually occurs in children aged 3-6 years. These patients have severe central nervous system involvement and only minimal somatic involvement. They commonly present with hyperactivity, mental deterioration, and developmental delay. Physical findings include coarse hair, hirsutism, mild hepatosplenomegaly, and enlarged head. Occasionally, mild dysostosis multiplex and joint stiffness are seen. By age 8-10 years, these patients are profoundly retarded with severely disturbed social behavior (eg, uncontrollable hyperactivity, destructive physical aggression). These patients usually survive into the second or third decade of life.
• MPS IV (Morquio syndrome): Deficiencies of two different enzymes leading to a severe form (MPS IV A) and a mild form (MPS IV B) are recognized. Orthopedic involvement is the primary finding in these patients, with preservation of intelligence and varying degrees of skeletal involvement. Spondyloepiphyseal dysplasia is the hallmark of this disease. Physical findings include genu valgum, short stature, spinal curvature, odontoid hypoplasia, and ligamentous laxity. Atlantoaxial instability is common in Morquio syndrome and can lead to severe myelopathy, paralysis, and death. Patients with the severe form do not survive beyond the third or fourth decade of life. Patients with the mild form have much slower progression of skeletal dysplasia and a normal life span.⁹
• MPS VI (Maroteaux-Lamy syndrome): Onset occurs in patients aged 1-3 years. Mild, intermediate, and severe types have been identified, all with the same enzyme deficiency. Features are very similar to Hurler syndrome, including corneal clouding, coarse facies, joint stiffness, skeletal deformities, and heart valvular disease. Intelligence, however, is normal. These patients may survive into the third decade of life. Most die from cardiopulmonary complications.
• MPS VII (Sly syndrome): This is a very rare condition, with fewer than 20 cases identified worldwide. Mild and severe forms have been identified. The severe form of MPS VII can be detected in the neonatal period associated with hydrops fetalis and hepatosplenomegaly, with death occurring within the first few months of life. Patients with the mild form survive into adolescence. The phenotype is similar to that of Hurler syndrome. Physical findings include corneal clouding, coarse facies, macrocephaly, metatarsus adductus, prominent sternum, pelvic hypoplasia, hepatosplenomegaly, and hernias.

Causes

• Defective activity of the lysosomal enzymes blocks the degradation process of mucopolysaccharides, leading to abnormal accumulation of heparan sulfate, dermatan sulfate, and keratan sulfate.
• All mucopolysaccharidoses are inherited as autosomal recessive disorders with the exception of Hunter syndrome (MPS II), which is inherited as sex-linked recessive.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to Be Considered

Morquio syndrome can be confused with spondyloepiphyseal dysplasia, which is a severe form of skeletal dysplasia. In fact, many skeletal dysplasias were falsely labeled as Morquio syndrome until the discovery in the early 1960s that Morquio syndrome is a lysosomal storage disease.

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Prenatal screening
• • Chorionic villus sampling: This test is performed around the ninth week of pregnancy and has become increasingly popular for the diagnosis of MPS.
  • Amniocentesis: Prenatal diagnosis of MPS conditions (with the exception of Hunter syndrome) can be made by measuring the enzyme activity in cultured amniotic cells. Amniocentesis commonly is performed in the 15th to 16th week of gestation. Heterozygote identification is important in Hunter syndrome and can be done with hair root analysis and single cell cloning of fibroblasts. However, these procedures are not widely available.
• Postnatal diagnosis: Urine analysis is useful because excessive urinary excretion of glycosaminoglycans is the basis for screening tests for MPS. Serum assays are useful because lysosomal enzymes can be assayed in serum, leukocytes, or cultured cells. These assays for different lysosomal enzymes are taken for all patients thought to have MPS.
• • MPS IH (Hurler syndrome)^{6, 10} 
    • Enzyme deficiency - Alpha-L-Iduronidase
    • Urinary glycosaminoglycan (GAG) - Dermatan sulfate, heparan sulfate
  • MPS I-H/S (Hurler-Scheie syndrome)
    • Enzyme deficiency - Alpha-L-Iduronidase
    • Urinary GAG - Dermatan sulfate, heparan sulfate
  • MPS IS (Scheie syndrome)
    • Enzyme deficiency - Alpha-L-Iduronidase
    • Urinary GAG - Dermatan sulfate, heparan sulfate
  • MPS II-A (Hunter syndrome, severe)⁷
    • Enzyme deficiency - Iduronate sulfatase
    • Urinary GAG - Dermatan sulfate, heparan sulfate
  • MPS II-B (Hunter syndrome, mild)⁷
    • Enzyme deficiency - Iduronate sulfatase
    • Urinary GAG - Dermatan sulfate, heparan sulfate
  • MPS III-A (Sanfilippo syndrome A)
    • Enzyme deficiency - Heparan N-sulfatase
    • Urinary GAG - Heparan sulfate
  • MPS III-B (Sanfilippo syndrome B)
    • Enzyme deficiency - N-acetylglucosaminidase
    • Urinary GAG - Heparan sulfate
  • MPS III-C (Sanfilippo syndrome C)
    • Enzyme deficiency - Acetyl-coenzyme A: Alpha-glucosamine-N-acetyltransferase
    • Urinary GAG - Heparan sulfate
  • MPS III-D (Sanfilippo syndrome D)
    • Enzyme deficiency - N-acetyl alpha-glucosamine-6-sulfatase
    • Urinary GAG - Heparan sulfate
  • MPS IV-A (Morquio syndrome A)
    • Enzyme deficiency: N-acetylgalactosamine-6-sulfatase
    • Urinary GAG: Keratan sulfate
  • MPS IV-B (Morquio syndrome B)
    • Enzyme deficiency - B-galactosidase
    • Urinary GAG - Keratan sulfate
  • MPS VI (Maroteaux-Lamy)
    • Enzyme deficiency - N-acetylgalactosamine-4-sulfatase
    • Urinary GAG - Dermatan sulfate
  • MPS VII (Sly syndrome)
    • Enzyme deficiency - B-glucuronidase
    • Urinary GAG - Dermatan sulfate, heparan sulfate

Imaging Studies

• Radiographs: Dysostosis multiplex refers to a constellation of skeletal abnormalities in MPS conditions diagnosed based on plain radiographs. Dysostosis multiplex is classic in Hurler syndrome (see Images 5, 7-8). These findings include the following:
• • Large skull with thickened calvaria, premature suture closure, j-shaped sella turcica, and shallow orbits
  • Abnormal spacing of teeth with dentigerous cysts
  • Short, thickened and irregular clavicles
  • Short, wide, and trapezoid shaped phalanges
  • Oar-shaped ribs
  • Anterior hypoplasia of the lumbar vertebrae with kyphosis
  • Poorly formed pelvis with small femoral heads and coxa valga
  • Enlarged diaphyses of long bones and irregular metaphyses
• CT scan of the cranium: This can be used to help diagnose hydrocephalus.
• Echocardiogram: This is a useful monitoring test for ventricular function and size in MPS patients with cardiovascular disease.

Other Tests

• Electroretinography is a diagnostic method to assess the presence of retinal involvement in patients with MPS.
• Audiologic assessment is performed to evaluate for hearing loss in MPS.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

Specific treatment or cure is limited for MPS. Management has been limited to supportive care and experimental treatment modalities. Routine assessment of multiple organ involvement is necessary to maintain the highest quality of life in these patients. Below are some of the medical and surgical treatment modalities that have been attempted for care of the patient with MPS. ^{5, 11, 12, 10, 8, 13}

Laronidase (Aldurazyme) is a polymorphic variant of the human enzyme alpha-L-iduronidase produced by recombinant DNA technology. It is indicated to treat MPS type I (Hurler and Hurler-Scheie forms). It increases catabolism of glycosaminoglycans (GAGs), which accumulate with MPS I. Laronidase therapy has shown to improve walking capacity and pulmonary function.

Idursulfase (Elaprase) is a purified form of human iduronate-2-sulfatase, a lysosomal enzyme. It hydrolyzes 2-sulfate esters of terminal iduronate sulfate residues from the GAGs dermatan sulfate and heparan sulfate in the lysosomes of various cell types. It is used to replace insufficient levels of the lysosomal enzyme iduronate-2-sulfatase in MPS II.^{14, 12, 10, 8}

• Hearing loss: Severe handicapping hearing loss is present in about 70% of patients with MPS. Routine audiologic assessment and management is extremely important in order to maintain the highest quality of life.
• Joint stiffness: Range of motion exercises at home are indicated to limit the progressive loss of motion that is commonly seen in these patients. Night splinting and occupational aids have also been helpful.
• Bone marrow transplantation (BMT) has been successful in the treatment of MPS conditions, especially Hurler syndrome. Children treated with BMT generally have an increased lifespan compared to untreated children. Untreated children commonly died of cardiorespiratory compromise in the first decade of life. However, the musculoskeletal condition (dysostosis multiplex) did not improve with BMT. Skeletal radiographs of children treated with BMT and those who are not treated typically look similar.¹³

Surgical Care

Surgical care for specific conditions includes the following:

• Hydrocephalus: Ventriculoperitoneal shunting is the surgical treatment of choice in the child with hydrocephalus. Some clinical improvement has been noted in these patients after shunting. However, neurologic dysfunction has not been significantly affected. Thus, early recognition of hydrocephalus and early shunting before the onset of severe neurologic involvement may play a role in the management of these patients.
• Corneal clouding: Corneal transplantation has been performed for severe cases, but long-term results are lacking.
• Cardiovascular disease: Valve replacement has been performed, but experience is only limited. Mitral and aortic valves are most affected.
• Obstructive airway disease: Sleep apnea is common in MPS and is defined as cessation of airflow through the mouth or nose for a period greater than 10-15 seconds. Tracheostomy has been attempted for management of severe apnea with good success. Patients with obstructive airway disease are at a significant risk for anesthesia. This is especially true for patients with atlantoaxial instability such as those with Morquio syndrome.
• Orthopedic conditions: Orthopedic surgeries include soft tissue and bony procedures. The most common soft tissue procedure done in these patients is carpal tunnel release. Soft tissue procedures about the hip, knee, and ankle for release of contractures have also been performed, although results have been poor. Hip containment surgeries, such as femoral and pelvic osteotomies, are sometimes necessary in these patients. Progressive valgus deformity at the knee may also require corrective osteotomy, usually of the proximal tibia. Kyphosis is progressive in many of these patients, especially at the thoracolumbar level and sometimes associated with thoracis scoliosis. Posterior spinal fusion is proved to prevent further progression. In the cervical spine, odontoid hypoplasia can be seen leading to atlantoaxial instability. Fusion from C1 to C3 can be helpful.

Consultations

Multispecialty care is mandatory for these patients and should include a pediatrician (internist), a neurologist, a cardiologist, an ophthalmologist, an audiologist, an orthopedic surgeon, and a physical and occupational therapist.

FOLLOW-UP

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Complications

• Hearing loss
• Joint stiffness
• Hydrocephalus
• Corneal clouding
• Cardiovascular disease
• Obstructive airway disease

Prognosis

• The prognosis varies depending on the type of MPS. Most of these patients have shortened life spans, and some of them die in infancy (see Physical).
• Bone marrow transplantation has some positive effects systemically, such as reduction in hepatosplenomegaly, airway obstruction, and cardiopulmonary disease. These effects have resulted in improved life span, and many of these patients survive beyond the first decade of life.

MISCELLANEOUS

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Although no clinically proven treatments have been available for MPS, various experimental studies have been performed. These include enzyme replacement via plasma exchange and fibroblast transplantation from healthy individuals. These procedures resulted in decrease in excretion of urinary mucopolysaccharides but did not convincingly cause clinical improvement. These procedures are quite invasive and very expensive; thus, they have not achieved popularity in the medical community.

Special Concerns

• Identification of female heterozygotes can be possible in Hunter syndrome. These females appear clinically healthy. Carrier detection is done using hair-root analysis and single cell cloning of fibroblast. However, these tests are not widely available at this time.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  An 8-year-old boy with Morquio syndrome and severe kyphoscoliosis. Courtesy of Dennis P. Grogan, MD.
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Media file 2:  A 7-year-old girl with Morquio syndrome and typical severe genu valgum. Courtesy of Dennis P. Grogan, MD.
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Media file 3:  Morquio syndrome; widened bases of phalanges with osteopenia. Courtesy of Bruce M. Rothschild, MD.
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Media file 4:  Morquio syndrome; lateral radiograph of thoracolumbar vertebrae illustrates vertebral body beaking. Courtesy of Bruce M. Rothschild, MD.
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Media file 5:  Hurler syndrome; lateral radiograph of thoracolumbar vertebrae illustrates vertebral plana. Courtesy of Bruce M. Rothschild, MD.
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Media file 6:  Morquio syndrome; anteroposterior radiograph of pelvis illustrates avascular necrosis of femoral head. Courtesy of Bruce M. Rothschild, MD.
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Media file 7:  Hurler syndrome; widened metaphyses and diaphyses with truncated distal portions forming a peg characterize this radiograph. Courtesy of Bruce M. Rothschild, MD.
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Media file 8:  Hurler syndrome; widened metaphyses and diaphyses with truncated distal portions forming a peg characterize this radiograph. Courtesy of Bruce M. Rothschild, MD.
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Media type:  X-RAY

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

1. Bassyouni HT, Afifi HH, el-Awadi MK. Mucopolysaccharidosis type I: clinical and biochemical study. East Mediterr Health J. Mar-May 2000;6(2-3):359-66. [Medline].
2. Jones KL. Storage disorders. In: Smith's Recognizable Patterns of Human Malformation. Philadelphia, Pa: WB Saunders Co; 1997:456-471.
3. Muenzer J. Mucopolysaccharidoses. Adv Pediatr. 1986;33:269-302. [Medline].
4. Tandon V, Williamson JB, Cowie RA. Spinal problems in mucopolysaccharidosis I (Hurler syndrome). J Bone Joint Surg Br. Nov 1996;78(6):938-44. [Medline].
5. Masterson EL, Murphy PG, O''Meara A, et al. Hip dysplasia in Hurler''s syndrome: orthopaedic management after bone marrow transplantation. J Pediatr Orthop. Nov-Dec 1996;16(6):731-3. [Medline].
6. Dupont C, Hachem CE, Harchaoui S, Ribault V, Amiour M, Guillot M. [Hurler syndrome: Early diagnosis and successful enzyme replacement therapy: A new therapeutic approach. Case report.]. Arch Pediatr. Jan 2008;15(1):45-49. [Medline].
7. Martin R, Beck M, Eng C, Giugliani R, Harmatz P, Muñoz V. Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome). Pediatrics. Feb 2008;121(2):e377-86. [Medline].
8. Wraith JE, Scarpa M, Beck M, Bodamer OA, De Meirleir L, Guffon N. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. Mar 2008;167(3):267-277. [Medline].
9. Menkès CJ, Rondot P. Idiopathic osteonecrosis of femur in adult Morquio type B disease. J Rheumatol. Nov 2007;34(11):2314-6. [Medline].
10. Tolar J, Grewal SS, Bjoraker KJ, Whitley CB, Shapiro EG, Charnas L. Combination of enzyme replacement and hematopoietic stem cell transplantation as therapy for Hurler syndrome. Bone Marrow Transplant. Nov 26 2007;[Medline].
11. Chan YL, Lin SP, Man TT. Clinical experience in anesthetic management for children with mucopolysaccharidoses: Report of ten cases. Acta Paediatr Taiwan. Sep-Oct 2001;42(5):306-8. [Medline].
12. Tomatsu S, Montaño AM, Ohashi A, Oikawa H, Oguma T, Dung VC. Enzyme replacement therapy in a murine model of Morquio A syndrome. Hum Mol Genet. Dec 3 2007;[Medline].
13. Guffon N, Souillet G, Maire I, et al. Follow-up of nine patients with Hurler syndrome after bone marrow transplantation. J Pediatr. Jul 1998;133(1):119-25. [Medline].
14. Clarke LA. Idursulfase for the treatment of mucopolysaccharidosis II. Expert Opin Pharmacother. Feb 2008;9(2):311-7. [Medline].

Article Last Updated: Mar 4, 2008