Overview

• Definition: Rare lysosomal storage disorders involving the accumulation of complex carbohydrates or lipids.
• Shared Features with MPS Disorders:
  • Developmental delay.
  • Organomegaly.
  • Dysostosis multiplex.
• Progressive Conditions: All are progressive with worsening symptoms over time.
• Current Treatment: No disease-specific therapies available currently.

Mucolipidoses

• Mucolipidosis I (Sialidosis):
  • Gene: NEU1
  • Encoded Protein: α-neuraminidase
  • Features: Progressive myoclonus, cherry-red spots, coarse facial features, ataxia.
• Mucolipidosis II/III (I-Cell Disease):
  • Gene: GNPTAB, GNPTG
  • Encoded Protein: UDP-N-acetylglucosamine-1-phosphotransferase
  • Features: Severe skeletal dysplasia, growth failure, developmental delay, joint contractures.
• Mucolipidosis IV:
  • Gene: MCOLN1
  • Encoded Protein: Mucolipin-1
  • Features: Corneal clouding, developmental delay, psychomotor regression.

Oligosaccharidoses

• α-Mannosidosis:
  • Gene: MAN2B1
  • Encoded Protein: α-mannosidase
  • Features: Immune deficiency, hearing loss, skeletal abnormalities.
• β-Mannosidosis:
  • Gene: MANBA
  • Encoded Protein: β-mannosidase
  • Features: Intellectual disability, skeletal deformities, recurrent infections.
• Fucosidosis:
  • Gene: FUCA1
  • Encoded Protein: Fucosidase
  • Features: Coarse facial features, angiokeratomas, spasticity.
• Galactosialidosis:
  • Gene: CTSA
  • Encoded Protein: Cathepsin A
  • Features: Cardiac involvement, hepatosplenomegaly, angiokeratomas.
• Salla Disease/Infantile Sialic Acid Storage Disease:
  • Gene: SLC17A5
  • Encoded Protein: Sialin
  • Features: Hypotonia, developmental delay, myopathy.
• Aspartylglucosaminuria:
  • Gene: AGA
  • Encoded Protein: Aspartylglucosaminidase
  • Features: Coarse features, mild to moderate intellectual disability, skeletal changes.
• Schindler Disease:
  • Gene: NAGA
  • Encoded Protein: α-N-acetylgalactosaminidase
  • Features: Intellectual disability, seizures, angiokeratomas.

Key Points

• Diagnosis: Clinical suspicion based on phenotype, confirmed via genetic testing and enzyme analysis.
• Management:
  • Supportive care (e.g., physical therapy, symptomatic treatment).
  • Multidisciplinary team approach (neurology, genetics, orthopedics, etc.).
• Future Directions: Research on enzyme replacement therapy and gene therapy is ongoing.