Lysosomal Storage Disease

Description

Lysosomal storage diseases occur due to inherited deficiencies of various lysosomal enzymes and this may be due to abnormalities in their synthesis, processing or cellular trafficking. The normal function of lysosomes is to degrade molecules within the cell and, when these chemical reactions are truncated by the absence of a key enzyme, the substrates of the reaction accumulate within the organelle. Since there is some redundancy in the pathways by which proteins are degraded, deficiencies in proteases do not usually result in clinical disease. Deficiencies in the nuclease enzymes are also not usually compatible with survival.

There are a large number of different lysosomal storage diseases in dogs and cats categorised according to the product which accumulates within cells. All of the storage disease are rare.

• Excess accumulation of metabolites in lysosomes
• Affects mainly nervous system
• Also affects growth of cartilage

Classification

Class	Defective Enzyme	Name of Disease
Sphingolipidosis	beta D gangliosidase beta D hexosaminidase beta D glucocerebrosidase beta D galactocerebrosidase Sphingomyelinase	GM1 Gangliosidosis GM2 Gangliosidosis Gaucher Disease Krabbe Disease Niemann-Pick Disease
Oligosaccharidosis
Mucopolysaccharidosis
Glycoproteinosis
Proteosis

Pathophysiology

The clinical syndrome produced in each of the lysosomal storage disease results from the aberrant storage of metabolites within cells. The storage diseases usually affect multiple organs but some, such as those that are caused by a defect in the myelin degradation pathway, may only cause neurological signs.

The mucopolysaccharidoses involve a failure to degrade glycosaminoglycans (major components of cartilage) and they often involve skeletal deformity.

Diagnosis

Clinical Signs

Many of the lysosomal storage diseases are associated with neurological signs.

Laboratory Tests

Lysosonal storage disease often result in changes in leucocytic morphology which can be detected on a blood smear.

Disease	Finding on blood smear

Other Tests

Since genetic techniques have become more widely available and easily performed, it is often possible to characterise the genetic defect directly by determining the sequence encoding enzymes thought to be deficient. However, it should be remembered that several lysosomal storage diseases result from alterations in post-translational processes such as cellular trafficking.

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(LSD)

• Occurs in many breeds of dogs and cats.
• Genetic defects give deficiencies of specific enzymes of degradation.
  • Disease only occurs in animals homozygous at the gene pair controlling enzyme activity.
    • The genes are co-dominant.
  • Enzyme activity is extremely low or entirely absent.
• Large amounts of waste products accumulate within cells.
  • Nervous system cells are predisposed.
  • Cells become engorged.
  • Normal function is prevented.

• Image 1, courtesy of Cornell Veterinary Medicine
  
• Image 2, courtesy of Cornell Veterinary Medicine
• Image 3, courtesy of Cornell Veterinary Medicine

Clinical Signs

• Nervous system cells are predisposed to the disease, and so progressive neurological signs predominate.
  • Develop between 2 weeks and 12 months of age.
  • The disease is ultimately fatal.
• For example, Siamese cats show:
  • Ganglisidosis
  • Mucopolysaccharidosis

Diagnosis

• Clinical signs are considered.
• Urine enzyme assays may be helpful.
• Post-mortem diagnosis is possible.
• More recently, gene tests have been available.