Genetics · MU Sofia

22. Lysosomal Diseases: Mucopolysaccharidoses, Sphingolipidoses, Mucolipidoses

Covers the three main groups of lysosomal storage diseases, starting with how defective enzymes lead to accumulation of glycosaminoglycans, sphingolipids and glycoproteins. It then goes through mucopolysaccharidoses such as Hurler, Hunter and Sanfilippo syndromes, followed by sphingolipidoses including Tay-Sachs, Niemann-Pick, Gaucher, Fabry and Krabbe diseases, and finally I-cell disease as an example of mucolipidosis. Each entry notes the enzyme defect, inheritance pattern and main features, with a diagnosis and management summary for the mucopolysaccharidoses.

Inside: 6 sections · 9 labelled pictures · 14 flashcards · 3 min

Topic 22 of 65 in the MU Sofia syllabus for Genetics (Medicine, Year 3). The free AceMed note covers it in 6 sections, about 465 words (3 min of reading), with 14 flashcards.

In this note

  1. Lysosomal Diseases: Mucopolysaccharidoses, Sphingolipidoses, Mucolipidoses
  2. I. Introduction
  3. II. Mucopolysaccharidoses (MPS)
  4. III. Sphingolipidoses
  5. IV. Mucolipidoses
  6. V. Clinical Relevance

I. Introduction

  • Lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders caused by deficiency of specific lysosomal enzymes or transport proteins.
  • Result: incomplete degradation of macromolecules (glycosaminoglycans, sphingolipids, glycoproteins) → accumulation inside lysosomes → cell dysfunction, organ damage.
  • Inheritance: mostly autosomal recessive, except some X-linked (e.g., Hunter syndrome, Fabry disease).
  • Major groups:
  1. 1. Mucopolysaccharidoses (MPS) – defective degradation of glycosaminoglycans (GAGs).
  2. 2. Sphingolipidoses – defective degradation of sphingolipids.
  3. 3. Mucolipidoses – defective degradation/transport of glycoproteins.

II. Mucopolysaccharidoses (MPS)

Pathogenesis

  • Defective lysosomal enzymes → impaired breakdown of GAGs (heparan sulfate, dermatan sulfate, keratan sulfate, chondroitin sulfate).
  • Accumulation → coarse facial features, organomegaly, skeletal deformities, developmental delay.

Major Types

1. Hurler Syndrome (MPS I-H)

  • Defect: α-L-iduronidase deficiency.
  • Inheritance: AR.
  • Features:
  • Coarse facies, hepatosplenomegaly, corneal clouding.
  • Developmental delay, dwarfism, skeletal dysplasia (dysostosis multiplex).
  • Death often by age 10 due to cardiopulmonary complications.

2. Hunter Syndrome (MPS II)

  • Defect: iduronate sulfatase deficiency.
  • Inheritance: X-linked recessive.
  • Features: similar to Hurler but no corneal clouding.
  • Onset later, milder course.

3. Sanfilippo Syndrome (MPS III)

  • Defects: several enzymes (heparan sulfate degradation).
  • Features: severe CNS degeneration, mild somatic features.

Diagnosis

  • Urine: ↑ GAGs.
  • Enzyme assays, genetic testing.

Management

  • Enzyme replacement therapy (ERT) for MPS I, II, VI.
  • HSCT for severe cases.
  • Supportive care for organ complications.

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