Lysosomal Storage Disorders Made Easy

Among the common lysosomal storage disorders:

  1. Two of them are Mucopolysaccharidoses (Hunter and Hurler syndrome)
  2. Pompe’s disease is Glycogen Storage Disease.
  3. Others are Sphingolipidoses.

Inheritance of Lysosomal Storage Diseases

All are inherited as Autosomal Recessive (AR) condition except:

  1. Hunter syndrome (X-linked recessive)
  2. Fabry’s disease (X-linked recessive)

Higher risk in Ashkenazi Jews

Mnemonic: Ashkenazi Jews Drink TaNG

  1. Tay-Sach’s disease
  2. Niemann Pick’s disease
  3. Gaucher’s disease

Enzyme Defects in Lysosomal Storage Diseases

I couldn’t create any mnemonics that could help me remember the enzymes involved in Lysosomal Storage Disease. I thought, best would be to memorize them:

lysosomal storage diseases enzyme defects

Lysosomal storage disordersEnzyme deficiencyAccumulating substance
Tay-Sachs diseaseHexosaminidase AGM2 ganglioside
Niemann-Pick diseaseSphingomyelinaseSphingomyelin
Gaucher’s diseaseGlucocerebrosidaseGlucocerebroside
Fabry diseaseAlpha-Galactosidase ACeramide trihexoside
Metachromatic leukodystrophyArylsulfatase ASulfatides
Krabbe’s disease (Globoid cell leukodystrophy)Beta-Galactocerebrosidase (Galactosylceramidase)Galactocerebroside
Hurler syndrome (Type I MPS)Alpha-L-iduronidaseDermatan and Heparan sulfate
Hunter syndrome (Type II MPS)Iduronosulfate sulfataseDermatan and Heparan sulfate

Few mnemonics:

  1. HurLer syndrome: α-L-iduronidase
  2. HunTer syndrome: Iduronate sulfaTase
  3. Fabry’s disease: alpha-galactosidase A (Fabulous AlphaGuy)
    • Beta-galactosidase is deficient in GM1 gangliosidosis.
  4. Gaucher’s disease: Glucocerebrosidase (G for G)
  5. Niemann-Pick’s disease: Sphingomyelinase (SpiN or No-Man Picks his nose with sPhinger)
  6. Metachromatic leukodystrophy: Arylsulfatase (ArMed)
  7. Krabbe’s disease: Beta-galactocerebrosidase
  8. Tay-Sach’s disease: Hexosaminidase A (taysaX lacks heXosaminidase A)
  9. Gaucher’s have “U” hence, lacks Glucocerebrosidase and Krabbe’s don’t have “U” hence, lacks Galactocerebrosidase.
pathogenesis of sphingolipidoses
A more detailed pathogenesis of sphingolipidoses.

Hurler vs Hunter Syndrome

The mode of inheritance and enzymes involved are different as mentioned earlier. Besides, other differences are:

  1. Hunter needs eyes to shoot: Hence, eyes are spared in Hunter syndrome while, corneal clouding is a feature of Hurler’s syndrome.
  2. Hunter’s are brainier: Mental retardation is seen in both but is more severe in Hurler syndrome.
  3. Gargoyle’s Hurl balls of fire: Gargoylism (Gargoyle facies is a feature of Hurler syndrome).

Hepatosplenomegaly is due to accumulation of dermatan and heparan sulfate and seen in both.

Other important facts:

  1. Mental retardation is absent in Morquio’s syndrome (MPS type IV).
  2. All mucopolysaccharidosis except San-fillipo syndrome cause growth retardation and short stature.
  3. Scheie is the mildest, Hurler-Scheie is intermeidate and Hurler syndrome is the severest form of MPS I.

Cherry-Red Spots in Sphingolipidoses

cherry red spot

  1. Tay-Sach’s Disease (GM2 gangliosidsosis type I)
  2. Niemann-Pick’s disease
  3. Metachromatic leukodystrophy
  4. Sandhoff disease (Globose accumulation due to lack of Hexosaminidase A and B preventing conversion of Globose into Ceramide trihexoside; GM2 gangliosidosis type II)
  5. Farber’s disease (not Fabry’s disease !!! – lack of Acid ceramidase intervening conversion of ceramide into Sphingosine)
  6. GM1 gangliosidosis (deficient beta-galactosidase blocking the conversion of GM1 ganglioside to GM2 ganglioside).

Mnemonic: Tay-Sach’s and Niemann-Pick’s both are hyphenated and have cherry red spots as feature.

Remember: Cherry red spots is not a feature of Fabry’s and Gaucher’s disease.

Hepatosplenomegaly in Sphingolipidoses

  1. Hepatosplenomegaly is present in those with cherry-red spots except: Tay-Sach’s disease
  2. Gaucher’s disease

Remember: Hepatosplenomegaly is not a feature of Tay-Sach’s disease and Fabry’s disease.

CNS involvement in Sphingolipidoses

CNS involvement is not a feature of Gaucher’s disease type I (most common form). However, type II and III do present with CNS involvement.

HepatosplenomegalyCNS symptoms and Cherry red spot
+
+Niemann-Pick’sGaucher’s
Tay-Sach’sSomething else

Macrocephaly and Microcephaly

  1. Macrocephaly: Tay-Sach’s disease
  2. Microcephaly and Optic atrophy: Krabbe’s disease (Globoid cell leukodystrophy)

Fabry’s disease

Mnemonic: FABRy

Fabry’s disease cause:

  1. Angiokeratomas on skin
  2. Blood vessel: Hypertensoin
  3. Renal failure

Cells in Sphingolipidoses

lysosomal storage disorders

  1. Niemann-Pick’s disease: Zebra bodies (Distended lysosomes containing lamellated figures in Electron Microscopy), Foam cells/macrophages
  2. Gaucher’s disease: Gaucher cells/macrophages (crumpled tissue paper appearance)
  3. Tay-Sach’s disease: Onion-skin layers of whorled membrane within lysosomes (Electron microscopy)
  4. Krabbe’s disease (Globoid cell leukodystrophy): multinucleated Globoid cells
  5. Metachromic leukodystrophy: PAS + macrophages, Hirsh-Peiffer reaction (Sulfatides bind to cresyl violet and gives brown color instead of purple).

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