MUCOPOLYSACCHARIDOSIS
 
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MUCOPOLYSACCHARIDOSIS

 

DEFINITION:

A group of disorders caused by a deficiency of lysosomal enzymes needed for the stepwise degradation of glycosaminoglycans (mucopolysaccharides).

EPIDEMIOLOGY:

  • incidence: ?
  • age of onset:
    • varies with type of Mucopolysaccharidosis (MPS)
  • risk factors:
    • familial - autosomal recessive and x-linked recessive (MPS-II)
      • chrom. #: varies with type of MPS
      • gene: 10 enzyme deficiencies known

PATHOGENESIS:

1. Background

  • each of the known MPS involves a deficiency of one of ten enzymes needed for the stepwise degradation of dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS) singly or in combinaation; chondroitin sulfate (CS) may also be affected
  • the disorders are chronic and progressive and often display a wide spectrum of clinical severity within one enzyme deficiency
  • the MPS are themselves degradation products derived by the proteolytic cleavage of proteoglycans

2. Historical Aspects

1917 Hunter (1917) and Hurler (1919)

  • first identified Syndromes on basis of coarse face and skeletal anomalies -> gargoylism

1929 Morquio

  • first described the Morquio type

1952 Brante

  • first suggested the term "Mucopolysaccaridosis"
  • demonstrated storage of MPS in liver and meninges
  • classified MPS as a storage disease

1957 Dorfman and Lorincz

  • first to measure elevation of MPS in the urine
  • of diagnostic significance
  • suggested that the different types of MPS based upon the different types of MPS excreted in the urine

1962 Scheie

  • first described the Scheie type

1963 Sanfilippo

  • first described the Sanfilippo type

1963 Maroteaux

  • first described the Maroteaux-Lamy type

1965 McKusick

  • classification of MPS based on biochemical, clinical, and genetic criteria
  • renewed in 1972 and 1975

1968 Van Hoof and Hers

  • described MPS as a lysosomal storage disease
  • suggested MPS caused by enzyme deficiencies

CLINICAL FEATURES:

1. Central Nervous System Manifestations

1. Progressive Neurologic Disease

2. Developmental Delay

3. Intellectural Impairment

4. Behavioural Problems

2. Musculoskeletal Manifestations

1. Facial

  • coarse facies with frontal bossing
  • prognathism, dolichocephaly
  • nose - depressed bridge, broad, flat, flared

2. Skeletal

  • joints - stiffness, contractures
  • kyphosis
  • short stature
  • carpal tunnel syndrome

3. Other Manifestations

1. Respiratory

  • chronic respiratory tract infections
  • recurrent otitis media

2. Cardiovascular

  • +/- congestive heart failure

3. Gastrointestinal

  • hepatomegaly/hepatosplenomegaly
  • umbilical and inguinal hernias
  • failure to thrive

4. Ophthalmologic

  • corneal clouding
  • visual impairment

5. ENT

  • hearing impairment

INVESTIGATIONS:

1. Diagnostic

  • specific enzyme deficiency detected in leukocytes and/or cultured skin fibroblasts
  • prenatal
    • enzyme deficiency detected in cultured chorionic villi or amniocytes

2. Urine (Screen)

  • 24 hour urine collection: elevated DS, HS, KS, and/or CS

3. Imaging Studies

  • dystostosis multiplex

MANAGEMENT:

1. Supportive

  • no treatments have been identified for any of the MPS's
  • usually need a multidisciplinary approach
    • Paediatrics, Neurology, Orthopedics, Cardiology, ENT,
    • Ophthalmology
    • genetic counselling

2. Prognosis

  • varies with the type of MPS

 

 

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