Hunter Syndrome (Mucopolysaccharidosis Type II) 

Updated: Apr 18, 2018
Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD 



Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a member of a group of inherited metabolic disorders collectively termed the mucopolysaccharidoses (MPSs). The MPSs are caused by a deficiency of lysosomal enzymes required for the degradation of mucopolysaccharides or glycosaminoglycans (GAGs). Eleven distinct single lysosomal enzyme deficiencies are known to cause 7 different and recognized phenotypes of MPS. All of the MPSs are inherited in an autosomal recessive fashion, except for Hunter syndrome, which is inherited as X-linked recessive.

In the early 1900s, Gertrud Hurler and Charles Hunter first described patients with MPSs, whose metabolic disorders now bear their names (MPS I [Hurler syndrome], MPS II [Hunter syndrome]); subsequent MPSs have been assigned numbers and eponyms loosely associated with the chronology and origin of their report. MPS II was first described by Charles Hunter in 1917. This X-linked recessive disorder results from the lysosomal enzyme deficiency of iduronate 2-sulfatase (also labeled as I2S deficiency or iduronate sulfatase deficiency [ISD]). Iduronate sulfatase deficiency leads to the subsequent GAG accumulation of heparan sulfate and chondroitin sulfate B (dermatan sulfate) in the body.

In 1917 at The Royal Society of Medicine Meeting in London, Charles Hunter, a Canadian Professor of Medicine, presented the medical histories of 2 brothers who were later diagnosed with Hunter syndrome. Sixteen years later, physicians Binswanger and Ullrich coined the term dysostosis multiplex to describe the constellation of skeletal findings specific to persons with MPS and other lysosomal storage disorders.

The following are skeletal abnormalities described in dysostosis multiplex:

  • A large skull with a J-shaped sella
  • Anterior hypoplasia of the thoracic and lumbar vertebral bodies
  • Hypoplasia of the pelvis with small femoral heads and coxa valga (a hip deformity in which the angle formed between the head and neck of the femur and its shaft is increased, usually above 135°)
  • Oar-shaped ribs (narrow at the vertebrae and widening anteriorly)
  • Diaphyseal and metaphyseal expansion of long bones with cortical thinning
  • Tapering of the proximal phalanges

In 1952, Brante isolated the stored mucopolysaccharides from hepatic and meningeal tissues in patients with MPS; hence, the term mucopolysaccharidoses was used to describe this family of diseases. In 1957, Dorfman and Lorincz developed clinical assays to detect urinary mucopolysaccharides. Neufeld et al, in the late 1960s, demonstrated that mucopolysaccharide accumulation in fibroblasts from patients with Hurler (MPS I) and Hunter (MPS II) syndromes could be corrected by co-culturing them with fibroblasts or tissue extracts from patients with a differently diagnosed MPSs. This led to the purification and subsequent identification of each defective lysosomal enzyme within the mucopolysaccharidoses syndromes.[1]

All MPSs share the following clinical hallmarks:

  • A chronic progressive clinical course with multisystem involvement
  • Several phenotypic features, such as coarse facial appearance, growth failure, and organomegaly
  • Laboratory findings such as excretion of urinary GAG fragments and leukocyte inclusion bodies
  • Radiographic abnormalities, eg, dysostosis multiplex

Patients with Hunter syndrome are distinguished from patients with other MPSs because of the male dominant pattern due to the X-linked recessive genetic transmission. Females in whom preferential inactivation of the non-altered paternal allele occurs can have features of Hunter syndrome. Also, corneal clouding is not observed in Hunter syndrome and is therefore a key absent distinguishing feature within the MPS syndromes.


Glycosaminoglycans (GAGs) are oligosaccharide components of proteoglycans (macromolecules that provide structural integrity and function to connective tissues). The underlying defect in the MPSs is the inability to degrade GAGs. The chronic progressive course is caused by the accumulation of partially degraded GAGs, with resulting thickening of tissue and compromising of cell and organ function over time. Some of the clinical manifestations of GAG accumulation include coarse facial features, corneal clouding, thickened skin, and organomegaly. Manifestations of abnormal cell function include syndromic intellectual disability, growth failure, and skeletal dysplasia.

GAGs accumulate in lysosomes and extracellular tissue and are excreted in the urine. The exact mechanism by which GAG accumulation leads to disease features is unknown but may involve interference in cellular trafficking of molecules, alteration of the extracellular matrix, and interference with cell signaling and cell receptor functions.[2]

The primary GAGs in tissues include dermatan sulfate, heparan sulfate, keratan sulfate, and chondroitin sulfate. They are composed of sulfated sugar and uronic acid residues (except keratin sulfate, which is composed of galactose-6-sulfate alternating with sulfated N-acetylglucosamine residues). GAGs are degraded in a stepwise fashion from the nonreducing end by a series of lysosomal enzymes. Depending on the specific enzyme deficiency, the catabolism of one or more GAGs may be blocked. Clinical features in patients vary depending on the tissue distribution of the affected substrate and the degree of enzyme deficiency.

Dermatan sulfate is found mostly in skin but is also found in blood vessels, heart valves, lungs, and tendons; thus, accumulation of this GAG results in a characteristic skin deposition, myxomatous valvular changes (mitral valve prolapse), and progressive restrictive lung disease. Heparan sulfate is an essential component of nerve cell membranes; therefore, accumulation causes progressive neurological deterioration. Keratan sulfate accumulation leads to skeletal deformities. Dermatan and heparan sulfate accumulate in patients with MPS II owing to the lack of lysosomal enzyme, iduronate sulfatase (IDS).[3]

Hunter syndrome is distinct from the other mucopolysaccharidoses in that it is genetically inherited as an X-linked recessive disorder. The genetic locus has been mapped to Xq28. The gene defective in this disorder encodes for IDS.[4, 5] To understand the pathogenesis of genetic disorders, animal models can give important clues. For Hunter syndrome, a MPS II mouse model has been engineered to further understand the disease process.[6, 7]



United States

Incidence is unknown at present, but estimates may soon be available, following the institution of metabolic newborn screening for lysosomal storage disorders. Development of newborn screening strategies is underway.[8]


The estimated incidence of MPS II widely varies. The estimated incidence is 1 case per 34,000 in Israel, 1 case per 111,000 in British Columbia, and 1 case per 132,000 in the United Kingdom.[9, 10, 11] Recent studies from Germany and the Netherlands report an overall incidence of 1 case in 140,000-330,000 live births, and, more specifically, 1 case per 77,000 male births.[12]


Two types of Hunter syndrome are recognized; a severe form, designated as type A (MPS IIA), and a milder form, designated as type B (MPS IIB). These forms represent the two ends of a clinical spectrum of severity. The distinction is clinically based because iduronate sulfatase (IDS) activity is equally depressed in the laboratory assay used to diagnose both types of Hunter syndrome.

MPS IIA, the severe type, has clinical features similar to those observed with Hurler syndrome, except that corneal clouding is not seen and multisystem involvement does not progress as quickly as seen in Hurler syndrome. In MPS IIA, clinical manifestations become evident in the first few years of life. Children are developmentally delayed and are often hearing impaired with progression to deafness.

Complications in older patients with MPS IIA include carpal tunnel syndrome with entrapment of the medial nerve and degenerative disease of the hips. Subsequent slow systematic somatic and neurologic progression ultimately leads to death in adolescence; however, some patients may live into their second and third decades of life. The cause of death is frequently cardiopulmonary failure secondary to upper airway obstruction and cardiovascular involvement. Incidence of sudden death is about 11%.[13]

Children with MPS IIB (mild type) resemble children with Hurler/Scheie (MPS IH/S) or Scheie syndromes (MPS IS). These children usually have normal intelligence. They may develop airway obstruction secondary to accumulation of mucopolysaccharide in the trachea and bronchi. Patients survive well into adulthood and may live into their seventh decade of life. Most patients will develop valvular heart disease.


Hunter syndrome is panethnic and rare; however, a higher incidence has been noted in the Jewish population living in Israel.


Inheritance is X-linked recessive, and affected males do not usually reproduce. The disorder is occasionally diagnosed in females consequent to skewed X-inactivation, with the active X carrying the mutation in the iduronate sulfatase (IDS) allele.[14]


MPS IIA is typically diagnosed in children aged 2-4 years. MPS IIB may not be diagnosed until adolescence or adulthood.




Type A mucopolysaccharidosis type II (MPS IIA) - severe form

Disease presentation usually occurs between age 2-4 years and is characterized by progressive neurological involvement and concurrent somatic effects.{ref1345-INVALID REFERENCE} Initial clinical features may include coarse facies, short stature, skeletal deformities, joint stiffness, developmental delay, and intellectual disability. Additional features at presentation or upon reevaluation may include hyperactivity, retinal degeneration, progressive hearing loss, recurrent ear infections, hepatomegaly, and carpal tunnel syndrome.

Communicating hydrocephalus can develop and can further contribute to neurological deterioration. The neurologic involvement is progressive and profound in the late stages of life (typically the second and third decades of life). Other features occasionally seen, especially in patients who are severely affected, are seizures and an overall phenotypic severity approaching that of Hurler syndrome (MPS I).

Valvular heart leaflets become dysfunctional owing to glycosaminoglycan (GAG) accumulation. A thickened myocardium eventually leads to coronary artery compromise, myocardial disease, and, in conjunction with airway disease, pulmonary hypertension.

The gastrointestinal system is also affected via autonomic dysregulation and, possibly, mucosal dysfunction, which causes chronic diarrhea in younger patients; marked constipation may be a problem in older patients.

Death is usually due to complications of obstructive airway disease, cardiac failure, or a combination of both.

Type B mucopolysaccharidosis type II (MPS IIB) – milder attenuated form

The presentation of MPS IIB typically occurs in adolescence or adulthood.[15, 16, 17, 18, 19, 20, 21]

Somatic involvement is distinguishable from that seen in patients with MPS IIA by the decreased rate of progression and the lesser degree of eventual handicap. Intelligence is usually preserved. Hearing impairment, joint stiffness, coarse facial features, upper airway disease, and carpal tunnel syndrome as seen in MPS IIA remain hallmarks in MPS IIB, but become evident over a more protracted time period.

Communicating hydrocephalus does not occur as often, although papilledema has been seen in the absence of increased intracranial pressure, suggesting a localized process involving the optic nerves.

Absence of corneal clouding is a feature that differentiates MPS IIA and MPS IIB from MPS I; however, there have been reports of patient with MPS II who have discrete corneal opacities viewed on slit-lamp examination. These opacities appear not to impair visual acuity. Retinal degeneration is seen to a lesser degree in MPS IIB.

Patients diagnosed with MPS IIB can live beyond the fifth decade of life. Death is often secondary to obstructive airway disease and cardiac failure, as is seen in patients with MPS IIA. 


Both MPS IIA and MPS IIB have deficient IDS activity. Distinguishing between these types is useful to clinically describe the extremes of MPS II disease spectrum.


Common presenting signs and symptoms in children with classic MPS IIA include progressive coarsening of facial features, short stature, joint stiffness, hepatosplenomegaly, and hernias. Children with MPS IIA are macrocephalic and tend to have severe intellectual disability. In MPS II, corneal opacities are absent; however other ocular findings occur and include an atypical retinal degeneration and a chronic form of papilledema that leads to visual impairment.[18, 19, 20] Hearing impairment progresses to profound deafness. This hearing loss may be either conductive or sensorineural but is often of a mixed type. Inspection of the oropharynx can reveal widely spaced teeth and an enlarged tongue. The enlarged tongue is more pronounced in children older than 5 years.

Phenotypically, persons with MPS IIA have a short neck, broad chest, a protuberant abdomen, hepatosplenomegaly, and an umbilical hernia. Musculoskeletal findings include dysostosis multiplex and thoracolumbar kyphosis, and the trunk appears short in length when compared to the length of the extremities. Joint mobility is decreased, and the fingers may have clawlike deformities. Patients tend to walk with a stiff gait. Short stature is usually not noted until after age 3 years. Data from the Hunter Outcome Survey indicated that patients follow an average height curve until age 9-10 years and then cease growing, subsequently falling in the height curve to less than the third percentile as they age.[12]

Children with MPS IIA and MPS IIB may have ivory-colored papular skin lesions that are symmetrically distributed on the upper back between the angles of the scapulae and posterior axillary lines, in the pectoral region, and on the lateral upper arms and thighs. These skin lesions, which develop in a reticular pattern and appear pebbly, are pathognomonic for the disease. The skin lesions typically develop before age 10 years. When biopsied, the pathology describes a dermal mucinosis. Additional dermatological findings include hypertrichosis, thickened skin, and multiple Mongolian spots. Hypertrichosis may result in synophrys. Mongolian spots in MPS II tend to be found in the lumbosacral region, are large, and can extend to both buttocks and onto the back.


Children with MPS IIB typically do not have intellectual disability but do have physical features that are similar to those of patients with MPS IIA. Skeletal manifestations in adults with MPS IIB may be only small carpal bones or mild dysplasia of the pelvis and femoral heads with premature osteoarthritis.

Growth patterns in 28 males with MPS IIB were cataloged from birth to 27 years, encompassing a 20-year period.[22] At birth, patients were typically larger than the general population and for the first 3 years of life. After age 3 years, there was a distinct, persistent decline in growth rates. In another study, 18 males with MSP II were studied before and after the start of enzyme replacement therapy (ERT). ERT seemed to improve growth rates in children, especially among those beginning ERT prior to age 10 years.[23]


MPS II (Hunter syndrome) differs from the other MPSs in that it is inherited in an X-linked recessive fashion. The remaining known MPSs are inherited in an autosomal recessive fashion. MPS II is due to deficiency or absence of the lysosomal enzyme, iduronate 2-sulfatase deficiency (IDS). The cytogenetic location for the IDS gene is Xq28.

Defects in the gene encoding iduronate sulfatase (IDS) are causative.[24] Molecular analysis shows a wide variety of defects in IDS that cause Hunter syndrome. No single mutation has a high frequency of occurrence. Identical mutations have been found in patients diagnosed with either MPS IIA or MPS IIB, implicating the contribution of other genetic or environmental modifiers on the phenotype.[25, 26]

Although no strong point mutation correlations between genotype and phenotype are recognized, patients with large genomic deletions or genomic rearrangements plus involvement of contiguous genes to the IDS gene phenotypically have severe disease. Patients with contiguous deletions have additional findings attributed to the other genes involved.[5, 27] Such contiguous gene deletions are identified in around 20% of patients with MPS II.[28, 29]

Skewed X-inactivation of the non-altered X chromosome in a heterozygous female can lead to clinical disease. Severity is related to the type of mutation on the active X chromosome, as is seen in male patients, and is also related to the ratio of altered to non-altered X chromosome activity in the female patient.[30]



Diagnostic Considerations

Carrier status of the mother determines the recurrence risk to the family and can be accurately determined by molecular testing once the IDS mutation in the male proband is identified.

Differential Diagnoses



Laboratory Studies

Clinical suspicion should take precedence over screening test results because laboratory results can vary.

Urine spot tests are readily available to screen for mucopolysaccharidoses (MPSs). These tests are associated with false-positive and false-negative results; testing more than one urine sample is recommended. Semiquantification of urinary GAGs can be obtained by spectrophotometric assays with dimethylmethylene blue.

Heparan sulfate, keratan sulfate (KS), and dermatan sulfate can be distinguished by electrophoretic techniques to narrow the diagnostic differential among the MPSs.A new enzyme-linked immunoassay (ELISA) technique has recently been shown to accurately quantify GAGs in urine (eg, dermatan and heparan sulfate excretion) and in blood.

Lysosomal enzymes are present in all cells except mature erythrocytes. The enzyme deficient in Hunter syndrome is iduronate-2-sulfatase. Iduronate sulfatase deficiency is determined by the direct enzymatic assay of leucocytes and fibroblasts. Academic medical facilities with expertise in metabolic genetics perform these assays on heparinized blood or fibroblasts cultured from a small (2-mm) skin biopsy.For prenatal diagnosis, enzyme activity can be measured in amniocytes or chorionic villi. Determination of the carrier state by enzyme analysis is not always possible because the range of enzyme activity in noncarriers and carriers overlaps. Carriers can be diagnosed by molecular analysis of the IDS gene. Usually the enzyme mutation is first identified in the affected proband.

GeneTests lists several institutions that offer enzymatic and mutation analysis for Hunter syndrome. Prior to obtaining laboratory samples from patients, it is important to obtain collection and transport instructions from the laboratory performing these assays.

Imaging Studies

A full skeletal survey should be obtained in a patient with suspected MPS. The following views are recommended:

  • Anteroposterior (AP) and lateral views of the skull with visualization of the sella
  • Flexion and extension radiographs of the cervical spine
  • AP and lateral views of the odontoid
  • AP and lateral views of the chest
  • Standing AP and lateral views of entire spine
  • Standing pelvis view with visualization of the femoral heads articulating with the acetabulum
  • Preferably, standing AP views of the lower extremities, including the entire femur, articulation with tibia (knees for genu valgus), and ankles
  • AP views of at least one foot, one hand, forearm, elbow in extension, humerus, and shoulder

CT scanning or MRI of the brain stem and cervical spine should be performed to evaluate for odontoid hypoplasia and cord compression. Additional cerebrospinal fluid (CSF) flow studies in both flexion and extension positions may be indicated in older patients. 

Other Tests

Other tests include the following:

  • Ophthalmologic examination with slit lamp: evaluation to assess visual acuity and corneal and retinal disease.
  • Audiology evaluation
  • Cardiac echocardiography and ECG
  • Airway evaluation: Assess for upper airway obstruction and sleep apnea and determine pulmonary function. [31]

Histologic Findings

Histologic examination of either peripheral granulocytes or bone marrow cells may show Alder-Reilly granulations. Peripheral lymphocytes exhibit metachromatic granules within vacuoles when stained with toluidine blue.



Medical Care

Although no curative treatment for lysosomal storage disorders is available, numerous treatment options are becoming available to improve the quality of life for these patients. The relevant enzyme, iduronate sulfatase (IDS) in the case of MPS II, can be administered to patients as enzyme replacement therapy (ERT).[32, 33, 34]  Bone marrow transplantation (BMT) is another treatment modality. Factors that affect patient outcome using these treatment modalities include the type of MPS, the donor genotype (in the case of BMT), and the age and degree of clinical involvement at the start of ERT or BMT.

In order to identify patients who might benefit from treatment before irreversible organ damage occurs, metabolic newborn screening for these disorders is being developed.[35] Gene therapy is a promising but inadequately developed modality of treatment. Difficulties with vector selection and efficiency of delivery persist; thus, this therapy is still in the early stages of development.


A study published in Journal of Inherited Metabolic Diseases addressed the long-term follow-up of patients with MPS II following BMT. Of the 16 children with MPS II who had undergone BMT, 15 of them continued to show marked deterioration in their intellectual abilities.[36] All 15 children had intelligence quotients that were below 50. Some children showed improvement in their somatic symptoms, such as a decrease in the coarseness of their facial features and an increase in the range of motion in their joints. Hearing deficits were not shown to improve after BMT.

IN 2000, the use of umbilical cord blood transplantation from an unrelated donor to treat a patient with MSP IIB was attempted.[37]


See Medication.

Enzyme replacement therapy (ERT) can help make the disease more manageable; however, it is not a cure for MPSs.

In 2006, the US FDA granted marketing approval for idursulfase (Elaprase), the first FDA-approved ERT for the treatment of MPS II. Elaprase targets the replacement of iduronate-sulfatase (IDS), the enzyme deficient in patients with MPS II. It is administered as a weekly IV infusion. In patients aged 16 months to 5 years, no data are available to demonstrate improvement in disease-related symptoms or in long-term clinical outcome; however, treatment with idursulfase has reduced spleen volume in patients with MPS II. Elaprase has also shown to improve walking capacity in patients aged 5 years and older. The safety and efficacy of Elaprase have not been established in children younger than 16 months.

Surgical Care

Many children with MPS II require surgical intervention for clinical complications of their disorder. These include intervention for chronic hydrocephalus, tracheostomy, nerve entrapment (carpal tunnel syndrome), abdominal wall hernias, and joint contractures.

Patients with MPS II should undergo anesthesia at a medical facility staffed with experienced and knowledgeable health care personnel. Complications can occur with airway management, postobstructive pulmonary edema, and reactive airway disease.


In 2008, the recognition and diagnosis of MPS II was reviewed in the American Academy of Pediatrics journal, Pediatrics.[38] This article clearly cited that the proper care for children with Hunter syndrome involves a multidisciplinary approach. The multidisciplinary team should include pediatricians, neurologists, orthopedists, otolaryngologists, ophthalmologists, audiologists, occupational and physical therapists, and geneticists and genetic counselors.



Medication Summary

Idursulfase, a purified form of human iduronate sulfatase (IDS) was approved by the US Food and Drug Administration (FDA) as an orphan drug in July 2006. It is distributed as Elaprase (Shire Human Genetics Therapies, Inc). FDA approval was based on the study of 96 patients in a double-blind, placebo-controlled study over one year.[39, 40] This study demonstrated improvement in a 6-minute walk test and reduction in liver and spleen volumes and urinary glycosaminoglycan (GAG) levels.

The extent to which enzyme replacement therapy (ERT) delays disease progression and whether or not it can prevent premature death is still unknown. Severely affected patients were not enrolled, and thus the benefit to them remains to be determined. ERT does not enter or affect the CNS and hence has no effect on cognitive function. Thus, the role of ERT in the management of Hunter syndrome is under debate.[41]


Class Summary

ERT is a life-long therapy that may improve the quality of life for patients with mucopolysaccharidosis type II (MPS II).

Idursulfase (Elaprase)

Purified form of human iduronate-2-sulfatase, a lysosomal enzyme. Hydrolyzes 2-sulfate esters of terminal IDS residues from the GAGs dermatan sulfate and heparan sulfate in the lysosomes of various cell types. Indicated for MPS II (Hunter syndrome) because it replaces the deficiency of iduronate-2-sulfatase in this disease. The drug is continued throughout life, and, thus, both the time and financial commitment can be extensive. Administration should be done by a health care professional in an experienced infusion center.



Further Outpatient Care

The Hunter Outcome Survey (HOS), funded by Shire HGT (Shire Human Genetics Therapies, Inc.), was established to better understand the variability and progression of Hunter syndrome (MPS II) and to monitor the long-term treatment effects of Elaprase. This ongoing study encourages patient participation in order to gather data regarding clinical response to ERT. Both MPS II patients receiving treatment and those who are not are encouraged to participate. As of May 2007, 263 patients from 16 countries were enrolled; 24% were being treated with ERT.[12]

Annual follow-up includes the following:

  • Echocardiography and ECG
  • Pulmonary function tests
  • Liver and spleen volume (MRI)
  • Skeletal survey
  • 6-minute walk test (every 6 mo)
  • Quality of life and pain assessment
  • Urinary glycosaminoglycan (GAG) level and iduronate sulfatase (IDS) antibody measurement
  • Audiography
  • Baseline sleep study, repeated as needed
  • CBC count, comprehensive metabolic panel, and routine urinalysis


Various complications may arise in the severe form of MPS II, including valvular heart disease and neurological complications.[42] Thickening of the tracheal walls may cause obstructive airway disease. Progression of abdominal organomegaly causes the abdominal wall to become markedly distended and hernias more prominent.

A study published in the Journal of Pediatrics evaluated the prevalence of cardiovascular manifestations in patients with Hunter syndrome. Using data from echocardiographic and electrocardiographic results from 102 patients who were enzyme replacement therapy–naïve in the Hunter Outcome Survey, the study found that, while valvular heart disease was the most common finding, left ventricular hypertrophy, elevated blood pressure, abnormal heart frequency, arrhythmia, and congestive heart failure were also noted.[43] The Hunter Outcome Survey (HOS) reports that 33% of patients develop hypertension.

Bone involvement occurs in MPS II, which may lead to short stature. All major joints, including the hips, knees, wrists, elbows, shoulders, and finger joints, become involved. This causes a decreased ability to pick up small objects, and, over time, walking becomes more difficult. The wrist is prone to carpal tunnel syndrome (CTS), which further decreases hand function.

A study published in the American Journal of Medical Genetics evaluated the prevalence, clinical manifestation, and nerve conduction profiles in 45 male patients with CTS and Hunter syndrome. A significant difference was noted in age between patients’ hands with normal, mild, moderate, and severe grades of CTS. It was also noted that the compound muscle action potential and sensory nerve action potential amplitudes of the median nerves decreased with age. These results suggest that Hunter syndrome may contribute to CTS in children.[44]

The Hunter Outcome Survey (HOS) reports that 84% of patients have neurological involvement (primarily behavioral and cognitive abnormalities).[12] Using data from neurobehavioral standardized assessments of patients with MPS II evaluated at the Program for Neurodevelopmental Function in Rare Disorders, one study sought to identify early clinical markers of neurologic involvement in MPS II. The study results noted that subsequent cognitive dysfunction was strongly associated with sleep disturbance, hyperactivity, behavior difficulties, seizurelike behavior, perseverative chewing behavior, and an inability to achieve bowel and bladder training; a new severity score was also developed, with a score greater than or equal to 3 indicating a high likelihood of developing CNS disease.[45]


The life expectancy in patients with the severe form (MPS IIA) is only about 10-15 years; however, those with the milder form (MPS IIB) may live well into the seventh or eighth decades of life with supportive care and management.

Following hematopoietic stem cell transplant (HSCT), the characteristic cutaneous papules tend to regress, and most are gone 3 months posttransplant.

Patient Education

Support groups serve as excellent resources for families and caregivers. Some of these support organizations include the following:

National Organization for Rare Disorders, Inc (NORD)

55 Kenosia Ave

PO Box 1968

Danbury, CT 06813-1968

Phone: (203) 744-0100

Toll-free: (800) 999-6673

Fax: (203) 798-2291

The Society for Mucopolysaccharide Diseases

46 Woodside Road


Buckinghamshire, HP6 6AJ

United Kingdom

Phone: 0845 389 9901

Fax: 0845 389 9902

National MPS Society

PO Box 14686

Durham, NC 27709-4686

Phone; (919) 806-0101 or (877) MPS-1001


Children Living with Inherited Metabolic Diseases (CLIMB)

The Quadrangle, Crewe Hall

Weston Road


Cheshire, CW1-6UR

England, United Kingdom

(127) 0 2 50221

Mucopolysaccharide & Related Diseases Society Australia Ltd. 

PO Box 623

Hornsby, NSW 2077


Phone: 612.9476.8411

Fax: 612.9476.8422


The Canadian Society for Mucopolysaccharide and Related Diseases Inc.

PO Box 30034 RPO Parkgate

North Vancouver BC, V7H 2YB

Phone: (604) 924-5130

Toll-free: (800) 667-1846

Fax: (604) 924-5131


Other sources of information include the following: