Updated: 10/11/2016

Mucopolysaccharidoses

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Review Topic
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Questions
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Evidence
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https://upload.orthobullets.com/topic/4101/images/muco table.jpg
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Introduction
  • A group of 13 metabolic syndromes caused by the absence or malfunctioning of lysosomal enzymes which break down glycosaminoglycans      
    • main forms include
      • Morquio syndrome and Sanfilippo syndrome most common
      • Hurler syndrome
      • Hunter syndrome
  • Pathophysiology
    • lysosomal storage disorders due to incomplete glycosaminoglycan breakdown products (mucopolysaccharides) accumulating and causing dysfunction in various organs
      • glycosaminoglycans are long sugar carbohydrate chains that help build bone, cartilage, tendons, corneas, skin and connective tissue
  • Associated conditions
    • orthopaedic manifestations 
      • proportionate dwarfism
      • increased rate of carpal tunnel syndrome 
      • C1-C2 instability  
      • delayed hip dysplasia
      • abnormal epiphyses
      • bullet-shaped phalanges
      • genu valgum
    • nonorthopaedic conditions
      • complex sugars in the urine
      • visceromegaly
      • corneal clouding
      • cardiac disease
      • deafness
      • mental retardation (except Morquio syndrome)
      • enlarged skull
  • Prognosis
    • bone marrow transplant improves life expectancy, but doesn't alter orthopaedic manifestations
Studies
  • Labs
    • urine test (toluidine blue-spot test) to analyze the excess mucopolysaccharides
    • skin fibroblast culture to test enzyme activity
    • chorionic villous sampling
Morquio Syndrome
  • Characterized by accumulation of keratan sulfate
    • interferes with the cartilage at the growth plate
    • presents at 18-24 months
  • Pathophysiology
    • Type A (galactosamine-6-sulfate-sulphatase deficiency)
    • Type B (beta-galactosidase deficiency)
  • Genetics
    • autosomal recessive
  • Prognosis
    • Type A is more severe
    • Type A and B survive into adulthood
  • Presentation
    • proportionate dwarfism
    • normal intelligence
    • waddling gait
    • genu valgum  
    • thoracic kyphosis
    • corneal clouding
  • Radiographs
    • thickened skull
    • wide ribs
    • vertebral beaking
    • coxa vara with unossified femoral head
    • bullet-shaped metacarpals
    • odontoid hypoplasia leading to cervical instability (obtain flexion-extension x-rays)   
    • thoracic kyphosis with platyspondia
  • Studies
    • keratan sulfate in urine
  • Treatment
    • decompression and cervical fusion
      • indications
        • myelopathy with C1-C2 instability
    • realignment osteotomies
      • restores plumb alignment to limb
      • malalignment commonly recurs
    • guided growth
      • attractive alternative to osteotomies, but there is a lack of evidence
Hurler Syndrome (Gargoylism)
  • The most severe mucopolysaccharidosis characterized by accumulation of dermatan sulfate
  • Pathophysiology
    • caused by alpha-L iduronidase deficiency
  • Genetics
    • inheritance pattern
      • autosomal recessive
  • Prognosis
    • death in first decade of life
  • Presentation
    • physical exam
      • proportionate dwarfism
      • progressive mental retardation
      • cloudy corneas
      • genu valgum
      • C1-C2 instability (25%)
      • carpal tunnel syndrome and finger triggering
  • Studies
    • dermatan sulfate in the urine
  • Treatment
    • bone marrow transplantation
      • indications
        •  in performed 1st year of life extend lifespan
      • but it doesn't change phenotypic orthopaedic changes
San Filippo Syndrome
  • characterized by accumulation of heparan sulfate
  • Pathophysiology
    • multiple enzyme deficiencies
  • Genetics
    • autosomal recessive
  • Prognosis
    • death in second decade of life
  • Presentation
    • mental retardation
    • proportionate dwarfism
    • clear cornea
  • Studies
    • heparan sulfate in the urine
  • Treatment
    • bone marrow transplant
      • has increased lifespan
Hunter Syndrome 
  • A mucopolysacharidosis characterized by accumulation of dermatan/heparan sulfate
  • Pathophysiology
    • sulpho-iduronate-sulphatase deficiency
  • Genetics
    • X-linked recessive
  • Prognosis
    • death by 2nd decade of life
  • Presentation
    • mental retardation
    • proportionate dwarfism
    • clear cornea
  • Studies
    • dermatan/heparan sulfate in urine
 

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(OBQ07.52) Morquio's syndrome is associated with all of the following anomalies EXCEPT: Review Topic

QID: 713
1

Accumulation of keratan sulfate

7%

(108/1500)

2

Genu valgum

9%

(130/1500)

3

Short stature

1%

(18/1500)

4

Odontoid hypoplasia

5%

(80/1500)

5

Triad of low hairline, webbed neck, and limited cervical spine range of motion

77%

(1160/1500)

ML 2

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

(OBQ09.23) Atlantoaxial instability due to hypoplasia of the odontoid is most commonly seen in which type of mucopolysaccharidosis? Review Topic

QID: 2836
1

Hurler's syndrome

11%

(176/1607)

2

Morquio's syndrome

72%

(1151/1607)

3

Hunter's syndrome

7%

(118/1607)

4

Sanfilippo's syndrome

4%

(67/1607)

5

Diastrophic dysplasia

5%

(87/1607)

ML 2

Select Answer to see Preferred Response

PREFERRED RESPONSE 2

(OBQ08.147) Children with lysosomal storage diseases have increased rates of which of the following disorders? Review Topic

QID: 533
1

Syringomyelia

15%

(263/1793)

2

Pectus excavatum

5%

(93/1793)

3

Macrognathism

11%

(196/1793)

4

Carpal tunnel syndrome

58%

(1033/1793)

5

Thoracic diastomyelia

11%

(204/1793)

ML 3

Select Answer to see Preferred Response

PREFERRED RESPONSE 4
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