Mucopolysaccharidosis Clinical Presentation

Updated: Feb 18, 2022
  • Author: Tarek Bittar, MD; Chief Editor: Jeffrey D Thomson, MD  more...
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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 (CSF) 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, [7] and tendon entrapment, such as trigger finger. [8, 9]


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. [8, 9, 10]

MPS I-H/S (Hurler-Scheie syndrome)

Hurler-Scheie syndrome 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)

The onset of Scheie syndrome 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 of Hunter syndrome 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. [11, 12, 13]


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.


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)

Sanfilippo syndrome 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 (CNS) 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) of Morquio syndrome 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 this 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. [14, 15]

MPS VI (Maroteaux-Lamy syndrome)

The onset or Maroteaux-Lamy syndrome 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. [16, 17]

MPS VII (Sly syndrome)

Sly syndrome is very rare, with an estimated frequency of 0.02 to 0.24 per 100,000 live births. [18] 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 of mucopolysaccharidosis include the following:

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