Lysosomal Storage Diseases

Lysosomal storage diseases

 Lysosomalstorage disorders (LSDs) arise from the incomplete digestion of macromolecules. Causing the lysosomes to become large and numerous enough to interfere with normal cell functions.

All lysosomal storage disorders are autosomal recessive except

  • Fabry's disease and
  • Hunters syndrome
These are x-linked recessive diseases.

Affected organs and lysosomal storage diseases depend on the tissue. Where most of the material to be degraded is found and where the degradation normally occurs.

Fabry's disease

Fabry's disease presents with -
  • Peripheral Neuropathy of the hands and feet.
  • Angiokeratomas, 
  • Cardiovascular disease
  • Renal disease.
  • Patients also have a 20-fold increased risk and stroke.

Fabry's disease is caused by a deficiency in α-galactosidase enzyme.

Gaucher's disease

Gaucher's disease presents with - 
  • Hepatosplenomegaly
  • Aseptic necrosis of the femur,
  • Bone crisis,
  • Pancytopenia or thrombocytopenia.

Gaucher's cells are macrophages that appear like crumpled paper.
Neurological symptoms occur in less frequent subtypes of gaucher's disease.

Gaucher's disease is caused by a deficiency in β-Glucocerebrosidase. This leads to an accumulation of glucocereboside.

Niemann-Pick disease

Niemann-pick disease presents with -
  • Progressive Neurodegeneration
  • Hepatosplenomegaly
  • Cherry red spots on the macula
  • Foam cells.
Niemann-pick disease is caused by deficiency in enzymes spihingomyelinase. This leads to an accumulation of sphingomyelin with the central nervous system involvement.

Tay-Sachs disease

Tay-sachs disease presents with -
  • Progressive Neurodegeneration,
  • Developmental delay,
  • Cherry red spots on the macula,
  • Lysosomes that are appear like onion skins
  • There is no hepatosplenomegaly.
Tay-sachs disease has a deficiency of Hexosaminidase A. This leads to an accumulation of GM2 Gangliosides.

Krabs disease

Krabs disease presents with -
  • Peripheral neuropathy,
  • Developmental delay,
  • Optic atrophy,
  • Fever and
  • Globoid cells,
  • Often at times it can present with irritability.

Krabs disease has a deficiency in galactocerebrosidase. This leads to an accumulation of galactocerebroside.

Metachromatic leukodystrophy

Metachromatic leukodystrophy presents with - 
  • Central and peripheral demonization with ataxia and dementia.
Metachromatic leukodystrophy has a deficiency of arylsulfatase A. This leads to an accumulation of cerebroside sulfate.

Hurler's syndrome

Hurler's syndrome presents with -
  • Developmental delay,
  • Gargoylism,
  • Airway obstruction,
  • Corneal clouding and
  • Hepatosplenomegaly.

  Hurler syndrome has a deficiency in α-L-iduronidase. This leads to an accumulation of heparan sulfate and Dermatan  sulfate. Deposits in coronary arteries leads to ischemic heart disease.

Hunter syndrome

Hunter syndrome presents as a mild form of hurler's syndrome. But also includes aggressive behavior and lacks corneal clouding.

  Hunter syndrome has a deficiency in it iduronate sulfatase. This leads to an accumulation of heparan sulfate and Dermatan sulfate.

Pompe's disease

Pompe's disease presents with -
  • Left ventricular hypertrophy which leads to outflow tract obstruction and cardiac failure.

  Pompe's disease has the deficiency in lysosomal α-1,4-glucosidase. This leads to glycogen deposits in the lysosomes.

I-cell disease

I-cell disease presents with -
  • Growth and developmental delay,
  • Course facial features,
  • Gingival hypertrophy and
  • Skeletal abnormalities.
  it's called I-cell due to cytoplasmic inclusions in fibroblasts.

It is caused by the inability to properly synthesize the mannose-6-phosphate tag required for targeting enzymes to lysosomes.

Treatments of Lysosomal storage diseases

The treatment of lysosomal storage diseases include
  • Enzyme replacement therapy
  • Substrate reduction therapy 
  • Molecular chaperone therapy.