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Updated: Jun 16 2021

Mucopolysaccharidoses

Images
https://upload.orthobullets.com/topic/4101/images/Clinical photo - colorado_moved.jpg
https://upload.orthobullets.com/topic/4101/images/Xray - genu valum - colorado_moved.jpg
https://upload.orthobullets.com/topic/4101/images/Clinical image_moved.jpg
https://upload.orthobullets.com/topic/4101/images/muco table.jpg
https://upload.orthobullets.com/topic/4101/images/Clinical photo_moved.jpg
  • summary
    • Mucopolysaccharidoses are a group of 13 metabolic syndromes caused by the absence or malfunctioning of lysosomal enzymes which break down glycosaminoglycans. Patients present with proportionate dwarfism, atlantoaxial instability, increased rate of carpal tunnel syndrome, cardiac abnormalities, mental retardation, and facial abnormalities. 
    • Diagnosis is made with urine tests to analyze the excess mucopolysaccharides, skin fibroblast culture to test enzyme activity, and intra-uterine chorionic villous sampling.
    • Treatment involves a multidisciplinary approach to improve and maintain function. Bone marrow transplantation improves life expectancy, but does not alter orthopaedic manifestations.
  • Etiology
    • 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
  • 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 
    • Pathophysiology
      • caused by alpha-L iduronidase deficiency
      • leads to accumulation of dermatan sulfate
    • 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
    • Pathophysiology
      • sulpho-iduronate-sulphatase deficiency
      • leads to accumulation of dermatan/heparan sulfate
    • Genetics
      • X-linked recessive
    • Prognosis
      • death by 2nd decade of life
    • Presentation
      • mental retardation
      • proportionate dwarfism
      • clear cornea
    • Studies
      • dermatan/heparan sulfate in urine
  • Prognosis
    • Bone marrow transplant improves life expectancy, but doesn't alter orthopaedic manifestations
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