Medical Genetics · MU Plovdiv

23. Enzymopathies and lysosomal storage diseases - lipidoses, mucopolysaccharidoses, glycogenoses. Clinical and genetic characteristics, MGС.

Inside: 9 sections · 15 labelled pictures · 27 flashcards · 7 min

Topic 23 of 33 in the MU Plovdiv syllabus for Medical Genetics (Medicine, Year 4). The free AceMed note covers it in 9 sections, about 972 words (7 min of reading), with 27 flashcards.

In this note

  1. Introduction
  2. I. Lysosomal storage diseases – introduction
  3. II. Mucopolysaccharidoses (MPS)
  4. III. Sphingolipidoses
  5. IV. Mucolipidoses
  6. V. Disorders of carbohydrate metabolism – introduction
  7. VI. Galactosemia
  8. VII. Glycogen storage disorders (GSDs)
  9. VIII. Clinical relevance

Introduction

This topic covers inherited enzyme defects: the lysosomal storage diseases (mucopolysaccharidoses, sphingolipidoses, mucolipidoses) and disorders of carbohydrate metabolism (galactosemia and the glycogen storage disorders), with their clinical and genetic characteristics and medical genetic counseling points.

I. Lysosomal storage diseases – 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:
  • Mucopolysaccharidoses (MPS) – defective degradation of glycosaminoglycans (GAGs).
  • Sphingolipidoses – defective degradation of sphingolipids.
  • 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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