Overview

• Mucopolysaccharidoses (MPS) are lysosomal storage disorders due to enzyme deficiencies impairing degradation of glycosaminoglycans (GAGs), also known as mucopolysaccharides.
• GAGs are complex sugar molecules found in connective tissues, skin, cartilage, cornea, liver, spleen, and vascular tissues.
• Examples: Dermatan sulfate, heparan sulfate, keratan sulfate, chondroitin sulfate, hyaluronic acid.
• Most MPS disorders are autosomal recessive, except MPS II (Hunter syndrome), which is X-linked.

Classification and Enzyme Deficiencies

MPS I and MPS II

• Clinical Features:

  • Severe forms present in preschool children with:
    • Developmental delay, short stature, recurrent infections.
    • Hepatosplenomegaly, coarse facial features (macrocephaly, thick eyebrows, macroglossia).
    • Progressive symptoms: Hearing loss, cardiac valve disease, skeletal contractures.
    • Dysostosis multiplex: Radiographic abnormalities like J-shaped sella turcica, oar-shaped ribs.
  • Milder forms have fewer somatic findings, normal intellect.
  • Complications: Corneal clouding, carpal tunnel syndrome, hydrocephalus, cervical instability.

• Diagnosis:

  • Elevated urinary mucopolysaccharides, enzyme activity assays, genetic testing.
  • Radiographs for dysostosis multiplex.

• Treatment:

  • Enzyme Replacement Therapy (ERT): Laronidase (MPS I), Idursulfase (MPS II).
  • Hematopoietic Stem Cell Transplant (HSCT): Stabilizes neurocognitive function in MPS I.
  • Multidisciplinary management.

MPS III (Sanfilippo Syndrome)

• Pathogenesis:
  • Defects in heparan sulfate metabolism.
• Clinical Features:
  • Neuropsychiatric predominance: Developmental delay, behavioral problems (aggression, hyperactivity).
  • Progression to seizures, spasticity, feeding difficulties, vegetative state.
  • Mild somatic features: Hepatosplenomegaly, cardiac valve thickening.
• Diagnosis:
  • Elevated urinary mucopolysaccharides, enzyme deficiency, genetic testing.
• Treatment:
  • No effective treatments yet; ongoing trials for CNS-targeted ERT.

MPS IV (Morquio Syndrome)

• Pathogenesis:
  • Enzyme deficiencies leading to skeletal dysplasia.
• Clinical Features:
  • Short stature, skeletal abnormalities (pectus carinatum, scoliosis, odontoid hypoplasia).
  • Non-skeletal features: Corneal clouding, hearing loss, cardiac dysfunction.
  • Normal intellect.
• Diagnosis:
  • Urine mucopolysaccharides (may be normal in older patients), enzymatic and genetic testing.
• Treatment:
  • ERT (Elosulfase alfa) improves endurance and reduces keratan sulfate accumulation.
  • Multispecialty care.

MPS VI (Maroteaux-Lamy Syndrome)

• Clinical Features:
  • Similar to MPS I and II but with normal intellect.
  • Features include short stature, coarse facies, cardiac valve abnormalities.
• Diagnosis:
  • Elevated urinary mucopolysaccharides, low arylsulfatase B activity, genetic testing.
• Treatment:
  • ERT (Galsulfase) improves growth, cardiac function, and joint mobility.

MPS VII (Sly Syndrome)

• Pathogenesis:
  • β-glucuronidase deficiency.
• Clinical Features:
  • Intellectual disability, coarse facies, joint contractures, hepatosplenomegaly.
  • Nonimmune fetal hydrops is a suggestive feature.
• Diagnosis:
  • Urinary mucopolysaccharides, β-glucuronidase activity, genetic testing.
• Treatment:
  • ERT (Vestronidase alfa) improves motor function and endurance.

General Principles of Management

• Diagnosis:
  • Initial screening with urine mucopolysaccharide quantitation.
  • Confirmatory tests: Enzyme assays and genetic testing.
• Treatment:
  • ERT slows disease progression; HSCT for neurocognitive stabilization in select cases.
  • Symptomatic management by multidisciplinary teams.
• Complications:
  • Regular monitoring for cardiac, orthopedic, neurological, and airway complications.