MORQUIO SYNDROME
 
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MORQUIO SYNDROME

 

DEFINITION:

A lysosomal storage disorder characterized by the accumulation of acid mucopolysaccharide (keratin sulphate) in peripheral tissues.

EPIDEMIOLOGY:

  • incidence: 1/100,000
  • age of onset:
    • 2-3 years of age
  • risk factors:
    • familial - autosomal recessive
      • MPS IVA - chrom.#: ?
        • gene: N-acetyl-galactosamine-6-sulfatase
      • MPS IVB - chrom.#: 3p21.33
        • gene: beta-galactosidase A
    • M = F

PATHOGENESIS:

1. Background

  • N-acetyl-galactosamine-6-sulfatase and beta-galactosidase A are lysosomal enzymes which catalyze the breakdown of keratin sulphate (KS)
  • disease first described in 1929 by Morquio and is now classified as Mucopolysaccharidosis (MPS) Types IVA and IVB

2. Genetic Defects

  • genetic defects -> deficiency of N-acetyl-galactosamine-6-sul-phase or beta-galactosidase activities -> incomplete degradation of keratin sulphate -> accumulation of KS in the cells of the musculoskeletal system causing severe musculoskeletal changes
  • mild to severe forms of Morquio Syndrome are not caused by unique enzyme deficiencies but by a wide spectrum of clinical manifestations found in both MPS IVA and IVB

CLINICAL FEATURES:

1. CNS Manifestations

1. Intelligence

  • normal

2. Others

  • atlantoaxial subluxation (due to a hypoplastic odontoid process with ligamentous laxity) -> cervical myelopathy -> spinal cord and nerve root compression -> leg weakness, paraplegia, paralysis

2. Musculoskeletal Manifestations

1. Facial Features

  • mild coarsening
  • midface hypoplasia with depressed nasal bridge and protrusion of the mandible (prominent lower face)
  • enamal hypoplasia in deciduous and secondary teeth with small teeth and frequent caries
  • short neck

2. Skeletal Features

  • growth retardation with short trunk and neck
  • short stature (dwarfism)
  • pectus carinatum deformity (pigeon chest)
  • flaring of the lower ribs
  • kyphoscoliosis
  • hyperlordosis (lumbar)
  • valgus deformity of the elbow
  • genu valgus
  • ulnar deviation of the wrist
  • ligamentous laxity with hypermobile joints and subluxation
  • waddling gait with tendency to fall
  • decreased joint mobility - hips, knees, and elbows
  • flat feet

3. Other Manifestations

1. Respiratory

  • restrictive lung disease due to restrictive chest wall movement secondary to kyphoscoliosis

2. Cardiovascular

  • cardiac valvular lesions
  • aortic regurgitation

3. Gastrointestinal

  • hepatomegaly/hepatosplenomegaly
  • inguinal hernias

4. Ophthalmologic

  • mild corneal clouding (slit lamp)

5. ENT

  • recurrent otitis media
  • conductive hearing loss

INVESTIGATIONS:

1. Diagnostic

  • deficiency of N-acetyl-galactosamine-6-sulfatase or beta-galactosidase activity in leukocytes and cultured skin fibroblasts
  • prenatal
    • deficiency of enzyme activity in cultured chorionic villi or amniocytes

2. Urine

  • 24 hour urine collection: elevated KS

3. Imaging Studies

1. Spinal X-Rays

  • odontoid hypoplasia
  • vertebrae
    • ovoid deformities
    • platyspondyly universalis (vertebral flattening)
    • central anterior (thoracic) or hook-shaped (lumbar) projections
    • increased intervertebral space

2. Skeletal X-Rays

  • epiphyseal deformities of the tubular bones (shortened long bones)
  • widened metaphyses
  • delayed ossification centres
  • wide acetabulae with progressive subluxation or dislocation of the femoral heads
  • osteoporosis
  • inclination of the distal ends of the radius and ulna towards each other
  • metacarpal deformities with short phalanges

MANAGEMENT:

1. Supportive

  • no treatment for the underlying disease
  • multidisciplinary approach
    • Paediatrics, Neurology, Orthopedics, ENT, Ophthalmology,
    • OT, PT
    • genetic counselling

2. Surgery

  • hernia repairs
  • upper cervical spinal fusion

3. Prognosis

  • life expectancy
    • adulthood (3rd - 4th decade)
    • may die earlier of cardiac or neurologic complications (i.e., cor pulmonale)
    • depends upon severity of the disease
  • adult height: 1 metre

 

 

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