Mucopolysaccharidosis 

Updated: Mar 06, 2018
Author: Tarek Bittar, MD; Chief Editor: Jeffrey D Thomson, MD 

Overview

Practice Essentials

Mucopolysaccharidosis (MPS) involves defective activity of the lysosomal enzymes, which blocks degradation of mucopolysaccharides and leads to abnormal accumulation of heparan sulfate, dermatan sulfate, and keratan sulfate. MPS can be subclassified as follows:

  • Hurler syndrome (MPS IH)
  • Hurler-Scheie syndrome (MPS I-H/S)
  • Scheie syndrome (MPS IS)
  • Hunter syndrome (MPS II)
  • Sanfilippo syndrome (MPS III)
  • Morquio syndrome (MP IV)
  • Maroteaux-Lamy syndrome (MPS VI)
  • Sly syndrome (MPS VII)

The image below depicts Morquio syndrome.

An 8-year-old boy with Morquio syndrome and severe An 8-year-old boy with Morquio syndrome and severe kyphoscoliosis. Courtesy of Dennis P. Grogan, MD.

Signs and symptoms

Patients with MPS have normal development initially, with abnormalities appearing in infancy or later in childhood. Those with multiple organ system involvement may have the following presentations:

  • CNS disease – Hydrocephalus; cervical spine myelopathy
  • Cardiovascular disease – Angina; valvular dysfunction; hypertension; congestive heart failure
  • Pulmonary disease – Airway obstruction, potentially leading to sleep apnea, severe respiratory compromise, or cor pulmonale
  • Ophthalmologic disease – Corneal clouding; glaucoma; chronic papilledema; retinal degeneration
  • Hearing impairment – Deafness
  • Musculoskeletal disease – Short stature; joint stiffness; symptoms of peripheral nerve entrapment

Findings from examination may include the following:

  • MPS IH – Corneal clouding, hepatosplenomegaly, skeletal deformities (dysostosis multiplex), coarse facial features, large tongue, prominent forehead, joint stiffness, and short stature; upper airway obstruction, recurrent ear infections, noisy breathing, and persistent nasal discharge; hirsutism, hearing loss, hydrocephalus, and mental retardation
  • MPS I-H/S - Milder features; normal intelligence and micrognathia; corneal clouding, joint stiffness, and heart disease
  • MPS IS - Aortic valve disease, corneal clouding, and joint stiffness; normal intelligence and stature
  • MPS II (severe) – Pebbly ivory skin lesions on the back, arms, and thighs; coarse facial features, skeletal deformities, and joint stiffness; retinal degeneration with clear cornea and hydrocephalus, mental retardation, and aggressive behavior
  • MPS II (mild form) – Similar features, but with much slower progression; normal intelligence and no hydrocephalus; hearing impairment and loss of hand function
  • MPS III – The most common MPS disorder; severe central nervous system (CNS) involvement and only minimal somatic involvement; coarse hair, hirsutism, mild hepatosplenomegaly, and enlarged head; occasionally, mild dysostosis multiplex and joint stiffness; eventually, by age 8-10 years, profound retardation with severely disturbed social behavior
  • MPS IV (severe) – Orthopedic involvement (eg, spondyloepiphyseal dysplasia) as the primary finding; preservation of intelligence; genu valgum, short stature, spinal curvature, odontoid hypoplasia, ligamentous laxity, and atlantoaxial instability
  • MPS IV (mild) – Much slower progression of skeletal dysplasia
  • MPS VI – Features very similar to MPS IH
  • MPS VII – Features similar to MPS IH

See Presentation for more detail.

Diagnosis

Prenatal screening studies that may be useful include the following:

  • Chorionic villus sampling
  • Amniocentesis

Postnatal diagnostic studies that may be helpful include the following:

  • Urinalysis, focusing on glycosaminoglycans (eg, dermatan sulfate, heparin sulfate, and keratin sulfate)
  • Serum assays for lysosomal enzymes (alpha-L-iduronidase, iduronate sulfatase, heparan N -sulfatase, N -acetylglucosaminidase, alpha-glucosamine- N -acetyltransferase, N -acetyl alpha-glucosamine-6-sulfatase, N -acetylgalactosamine-6-sulfatase, N -acetylgalactosamine-6-sulfatase, B-galactosidase, N -acetylgalactosamine-4-sulfatase, and B-glucuronidase)

Imaging studies that may be warranted are as follows:

  • Plain radiography (to detect dysostosis multiplex)
  • Computed tomography (CT) of the cranium (to help diagnose hydrocephalus)
  • Echocardiography (to monitor ventricular function and size in MPS patients with cardiovascular disease)
  • Magnetic resonance imaging (MRI; to evaluate spinal involvement)

Other tests to be considered are as follows:

  • Electroretinography
  • Audiologic assessment

See Workup for more detail.

Management

Specific treatment or cure is limited for MPS. Management has been limited to supportive care and experimental treatment modalities. Medical treatment modalities include the following:

  • Laronidase
  • Idursulfase
  • Elosulfase alfa
  • Vestronidase alfa

Surgical care for specific conditions may include the following:

  • Hydrocephalus – Ventriculoperitoneal shunting
  • Corneal clouding – Corneal transplantation
  • Cardiovascular disease – Valve replacement
  • Obstructive airway disease – Tracheostomy
  • Orthopedic conditions – Carpal tunnel release; soft tissue procedures to release hip, knee, and ankle contractures; hip containment surgeries; corrective osteotomy for progressive valgus deformity at the knee; posterior spinal fusion

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.

See Treatment and Medication for more detail.

Background

Mucopolysaccharides consist of glycosaminoglycans (GAGs) attached to a link protein with a hyaluronic acid core. Lysosomal enzymes degrade these macromolecules into smaller components. Mucopolysaccharidosis (MPS) involves defective activity of these enzymes, which blocks degradation of mucopolysaccharides. This incomplete degradation process leads to abnormal accumulation of heparan sulfate, dermatan sulfate, and keratan sulfate, and the abnormal accumulation of these compunds interferes with cell function.

Different forms of MPS were described separately throughout the 20th century. Their clinical presentations vary, depending on the type of enzyme defect and the glycoprotein accumulated. (See Lysosomal Storage Disease and Madelung Deformity.)

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. MPS can be subclassified according to the type and amount of substance that accumulates, as follows[1, 2, 3] :

  • Hurler syndrome (MPS IH) (see the first three images below)
  • Hurler-Scheie (MPS I-H/S)
  • Scheie syndrome (MPS IS)
  • Hunter syndrome (MPS II)
  • Sanfilippo syndrome (MPS III)
  • Morquio syndrome (MP IV) (see the fourth through eighth images below)
  • Maroteaux-Lamy syndrome (MPS VI)
  • Sly syndrome (MPS VII)
Hurler syndrome; lateral radiograph of thoracolumb Hurler syndrome; lateral radiograph of thoracolumbar vertebrae illustrates vertebral plana. Courtesy of Bruce M. Rothschild, MD.
Hurler syndrome; widened metaphyses and diaphyses Hurler syndrome; widened metaphyses and diaphyses with truncated distal portions forming a peg characterize this radiograph. Courtesy of Bruce M. Rothschild, MD.
Hurler syndrome; widened metaphyses and diaphyses Hurler syndrome; widened metaphyses and diaphyses with truncated distal portions forming a peg characterize this radiograph. Courtesy of Bruce M. Rothschild, MD.
An 8-year-old boy with Morquio syndrome and severe An 8-year-old boy with Morquio syndrome and severe kyphoscoliosis. Courtesy of Dennis P. Grogan, MD.
A 7-year-old girl with Morquio syndrome and typica A 7-year-old girl with Morquio syndrome and typical severe genu valgum. Courtesy of Dennis P. Grogan, MD.
Morquio syndrome; widened bases of phalanges with Morquio syndrome; widened bases of phalanges with osteopenia. Courtesy of Bruce M. Rothschild, MD.
Morquio syndrome; lateral radiograph of thoracolum Morquio syndrome; lateral radiograph of thoracolumbar vertebrae illustrates vertebral body beaking. Courtesy of Bruce M. Rothschild, MD.
Morquio syndrome; anteroposterior radiograph of pe Morquio syndrome; anteroposterior radiograph of pelvis illustrates avascular necrosis of femoral head. Courtesy of Bruce M. Rothschild, MD.

Etiology

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 forms of MPS are inherited as autosomal recessive disorders, with the exception of Hunter syndrome (MPS II), which is inherited as a sex-linked recessive disorder.

Epidemiology

Worldwide, the prevalence of all types of MPS is 1 case in 16,000-30,000 births. MPS III accounts for 80% of cases.

The 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.

All mucopolysaccharidoses are inherited as autosomal recessive disorders, with the exception of Hunter syndrome (MPS II); thus, all patients with Hunter syndrome are males.

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

Prognosis

The prognosis varies, depending on the type of MPS. Most of these patients have shortened life spans, and some die in infancy. 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.

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.

 

Presentation

History

Patients with mucopolysaccharidosis (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.

Central nervous system 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. (See Hearing Impairment.)

Musculoskeletal disease

Short stature is seen in all MPS conditions except MPS IS. Joint stiffness is a common feature in MPS, with the exception of MPS IV, in which joints demonstrate hyperlaxity. Other musculoskeletal presentations include symptoms of peripheral nerve entrapment, such as carpal tunnel syndrome,[4] and tendon entrapment, such as trigger finger.[5, 6]

Physical Examination

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.[5, 6, 7]

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.[8, 9, 10]

Severe

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.

Mild

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, differentiated on the basis of 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 of the syndrome 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.[11, 12]

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 those of 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.[13, 14]

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.

Complications

Complications of mucopolysaccharidosis include the following:

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

DDx

Diagnostic Considerations

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

Laboratory Studies

Antenatal screening

Chorionic villus sampling is performed around week 9 of pregnancy and has become increasingly popular for the diagnosis of mucopolysaccharidosis (MPS).

Antenatal 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 (GAGs) 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.

Assays for MPS IH (Hurler syndrome) are as follows[7, 15] :

  • Enzyme deficiency - Alpha-L-Iduronidase
  • Urinary glycosaminoglycan (GAG) - Dermatan sulfate, heparan sulfate

Assays for MPS I-H/S (Hurler-Scheie syndrome) are as follows:

  • Enzyme deficiency - Alpha-L-Iduronidase
  • Urinary GAG - Dermatan sulfate, heparan sulfate

Assays for MPS IS (Scheie syndrome) are as follows:

  • Enzyme deficiency - Alpha-L-Iduronidase
  • Urinary GAG - Dermatan sulfate, heparan sulfate

Assays for MPS II-A (Hunter syndrome, severe)[8]  are as follows:

  • Enzyme deficiency - Iduronate sulfatase
  • Urinary GAG - Dermatan sulfate, heparan sulfate

Assays for MPS II-B (Hunter syndrome, mild)[8]  are as follows:

  • Enzyme deficiency - Iduronate sulfatase
  • Urinary GAG - Dermatan sulfate, heparan sulfate

Assays for MPS III-A (Sanfilippo syndrome A) are as follows:

  • Enzyme deficiency - Heparan N -sulfatase
  • Urinary GAG - Heparan sulfate

Assays for MPS III-B (Sanfilippo syndrome B) are as follows:

  • Enzyme deficiency - N-acetylglucosaminidase
  • Urinary GAG - Heparan sulfate

Assays for MPS III-C (Sanfilippo syndrome C) are as follows:

  • Enzyme deficiency - Acetyl-coenzyme A: Alpha-glucosamine- N-acetyltransferase
  • Urinary GAG - Heparan sulfate

Assays for MPS III-D (Sanfilippo syndrome D) are as follows:

  • Enzyme deficiency - N-acetyl alpha-glucosamine-6-sulfatase
  • Urinary GAG - Heparan sulfate

Assays for MPS IV-A (Morquio syndrome A) are as follows:

  • Enzyme deficiency - N-acetylgalactosamine-6-sulfatase
  • Urinary GAG - Keratan sulfate

Assays for MPS IV-B (Morquio syndrome B) are as follows:

  • Enzyme deficiency - B-galactosidase
  • Urinary GAG - Keratan sulfate

Assays for MPS VI (Maroteaux-Lamy syndrome) are as follows:

  • Enzyme deficiency - N-acetylgalactosamine-4-sulfatase
  • Urinary GAG - Dermatan sulfate

Assays for MPS VII (Sly syndrome) are as follows:

  • Enzyme deficiency - B-glucuronidase
  • Urinary GAG - Dermatan sulfate, heparan sulfate

Imaging Studies

Dysostosis multiplex refers to a constellation of skeletal abnormalities in MPS conditions diagnosed on the basis of plain radiography. Dysostosis multiplex is classic in Hurler syndrome (see the images below). 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
Hurler syndrome; lateral radiograph of thoracolumb Hurler syndrome; lateral radiograph of thoracolumbar vertebrae illustrates vertebral plana. Courtesy of Bruce M. Rothschild, MD.
Hurler syndrome; widened metaphyses and diaphyses Hurler syndrome; widened metaphyses and diaphyses with truncated distal portions forming a peg characterize this radiograph. Courtesy of Bruce M. Rothschild, MD.
Hurler syndrome; widened metaphyses and diaphyses Hurler syndrome; widened metaphyses and diaphyses with truncated distal portions forming a peg characterize this radiograph. Courtesy of Bruce M. Rothschild, MD.

Computed tomography (CT) of the cranium can be used to help diagnose hydrocephalus.

Echocardiography is a useful monitoring test for ventricular function and size in MPS patients with cardiovascular disease.

Magnetic resonance imaging (MRI) is valuable for evaluation of spinal involvement in MPS VI.[16]

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.

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

 

Treatment

Medical Care

Specific treatment or cure is limited for mucopolysaccharidosis (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.[6, 17, 18, 15, 9, 19, 20]

Laronidase 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 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.[21, 18, 15, 9]

Elosulfase alfa is approved by the US Food and Drug Aministration (FDA) for patients with Morquio A syndrome (mucopolysaccharidosis type IVA [MPS IVA]). A study by Hendriksz et al found evidence to suggest that long-term use of this agent is associated with partial recovery of functional abilities in these patients.[22]

Vestronidase alfa is approved by the FDA for MPS VII.[23]

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.

Range-of-motion (ROM) 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.[19]

Surgical Care

Patients with mucopolysaccharidosis often require multiple common and uncommon surgical procedures and have a high postoperative mortality because of underlying respiratory and cardiac diseases.[24] 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 longer 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 surgical procedures 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, though results have been poor. Progressive hip subluxation, genu valgum, and ankle valgus are common. Hip containment procedures (eg, femoral and pelvic osteotomies) are sometimes necessary in these patients.[25, 26] Progressive valgus deformity at the knee can be addressed with "guided growth" techniques. Severe deformities may also necessitate corrective osteotomy, usually of the proximal tibia. Ankle valgus can be also be treated with guided growth techniques.

Kyphosis is progressive in many of these patients, especially at the thoracolumbar level and sometimes associated with thoracic scoliosis.[27] 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 the following:

  • Pediatrician (internist)
  • Neurologist
  • Cardiologist
  • Ophthalmologist
  • Audiologist
  • Orthopedic surgeon
  • Physical and occupational therapist
 

Medication

Metabolic & Endocrine, Other

Vestronidase alfa-vjbk (Mepsevii)

Enzymes, Metabolic

Idursulfase (Elaprase)

Elosulfase alfa (Vimizim)