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Lysosomal storage diseases

Last updated: December 11, 2020

Summary

Lysosomal storage diseases are a group of inherited metabolic disorders caused by a deficiency of specific enzymes. This causes an accumulation of abnormal substances that are usually degraded within lysosomes, resulting in cell damage and death. These substances include specific lipids and glycoproteins such as sphingolipids, glycosaminoglycans, and gangliosides, among others. Lysosomal storage diseases have a progressive course and, depending on the exact disease and subtype, can also be fatal in early childhood.

Overview

Overview of lysosomal storage diseases
Disease Inheritance Pathophysiology Clinical features Diagnostic findings
Sphingolipidoses

Gaucher disease

Krabbe disease

Tay-Sachs disease

Fabry disease

Metachromatic leukodystrophy
  • -
Niemann-Pick disease
Mucopolysaccharidoses
Hurler syndrome
  • Corneal clouding
Hunter syndrome
  • Aggressive behavior
Mucolipidoses
I-cell disease
  • -
Other
Adrenoleukodystrophy
  • -

Sphingolipidoses

Sphingolipidoses are a group of lysosomal storage diseases caused by inherited deficiencies of lysosomal enzymes leading to alteration of sphingolipid catabolism. This will eventually lead to accumulation of pathologic cellular inclusions and cell damage, ultimately resulting in cell death. There are three main types of pathologic cellular inclusions:

Gaucher disease

“The Girl HaS Painted A Bone Meticulously on a Crumpled Tissue Paper:” Glucocerebrosidase, HepatoSplenomegaly, Pancytopenia, Avascular necrosis of the femur, Bone crises, Macrophage inclusions that resemble crumpled tissue paper.

Krabbe disease

Tay-Sachs disease

  • Etiology: autosomal recessive inherited disease [5]
  • Epidemiology: : more common in the Ashkenazi Jewish population [6]
  • Pathophysiology: hexosaminidase A deficiency → intracellular accumulation of GM2 ganglioside → progressive neurodegeneration
  • Clinical features: Rapid reduction of physical and mental abilities begins around the age of 3–6 months [5]
  • Diagnostics: lysosomes with onion-skin appearance
  • Treatment: supportive

“After they Hexed Tay's Sax, his playing became deficient.”

Fabry disease

FABRYC: Foamy urine (Fabry nephropathy), α-galactosidase A deficiency/Angiokeratomas, Burning pain in hands and feet, Really sweaty/dry, YX genotype (male), Cardio-Cerebrovascular disease/Ceramide trihexoside accumulation.

Metachromatic leukodystrophy

Niemann-Pick disease

No Man Pictures the Sphinx Proudly Holding Cherries:” Niemann-Pick disease (Sphingomyelinase deficiency, Progressive neurodegeneration, Hepatosplenomegaly, Cherry-red spots in the macula).

Mucopolysaccharidoses

Mucopolysaccharidoses are a group of metabolic disorders that result in the impaired breakdown of glycosaminoglycans (previously known as mucopolysaccharides), due to mutations in lysosomal enzymes. At least nine different types of mucopolysaccharidosis have been identified. The two most common conditions are Hurler syndrome and Hunter syndrome. [13][14]

Overview of the most common mucopolysaccharidoses
Hurler syndrome (mucopolysaccharidosis type I) Hunter syndrome (mucopolysaccharidosis type II)
Inheritance
Pathophysiology
Clinical features
Diagnostics
Treatment

Hunters with good eyesight will catch the aggressive chupacabra active in TeXas:” Hunter syndrome (no corneal clouding, aggressive behavior, carpal tunnel syndrome, hyperactivity, and X-linked recessive inheritance).

Mucolipidosis

Mucolipids are complex lipid polymers that contain sialic acid or a related substance. Mucolipidoses were originally phenotypically confused with the mucopolysaccharidoses. However, the storage material in tissues includes not only mucopolysaccharides but also lipids. Additionally, glycosaminoglycans are not present in the urine of patients with mucolipidosis, while patients affected by mucopolysaccharidoses may have mucopolysacchariduria. [15]

The four main types of mucolipidosis include:

I-cell disease

References

  1. Krabbe disease. https://ghr.nlm.nih.gov/condition/krabbe-disease. Updated: January 23, 2018. Accessed: January 24, 2018.
  2. Hexosaminidase A Deficiency.
  3. Gross SJ, Pletcher BA, Monaghan KG, Professional Practice and Guidelines Committee.. Carrier screening in individuals of Ashkenazi Jewish descent.. Genet Med. 2008; 10 (1): p.54-6. doi: 10.1097/GIM.0b013e31815f247c . | Open in Read by QxMD
  4. Fabry Disease.
  5. Arylsulfatase A Deficiency.
  6. Acid Sphingomyelinase Deficiency.
  7. Niemann-Pick Disease Type C.
  8. Levran O, Desnick RJ, Schuchman EH. Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients.. Proc Natl Acad Sci U S A. 1991; 88 (9): p.3748-52. doi: 10.1073/pnas.88.9.3748 . | Open in Read by QxMD
  9. Schuchman EH, Desnick RJ. Types A and B Niemann-Pick disease.. Mol Genet Metab. 2016; 120 (1-2): p.27-33. doi: 10.1016/j.ymgme.2016.12.008 . | Open in Read by QxMD
  10. Matalon R, Matalon KM. The Mucolipidoses. Elsevier ; 2015 : p. 365-368
  11. Kliegman R, Stanton B, St. Geme J, Schor N. Nelson Textbook of Pediatrics. Elsevier ; 2015
  12. White KK. Orthopaedic aspects of mucopolysaccharidoses. Rheumatology (Oxford). 2011; 50 (Suppl 5): p.v26-v33. doi: 10.1093/rheumatology/ker393 . | Open in Read by QxMD
  13. Cathey SS, Leroy JG, Wood T, et al. Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands.. J Med Genet. 2010; 47 (1): p.38-48. doi: 10.1136/jmg.2009.067736 . | Open in Read by QxMD
  14. Gaucher Disease.
  15. Balwani M, Fuerstman L, Kornreich R, Edelmann L, Desnick RJ. Type 1 Gaucher disease: significant disease manifestations in "asymptomatic" homozygotes.. Arch Intern Med. 2010; 170 (16): p.1463-9. doi: 10.1001/archinternmed.2010.302 . | Open in Read by QxMD
  16. Weiss K, Gonzalez A, Lopez G, Pedoeim L, Groden C, Sidransky E. The clinical management of Type 2 Gaucher disease.. Mol Genet Metab. 2015; 114 (2): p.110-122. doi: 10.1016/j.ymgme.2014.11.008 . | Open in Read by QxMD
  17. Le T, Bhushan V, Sochat M, Chavda Y. First Aid for the USMLE Step 1 2017. McGraw-Hill Education ; 2017
  18. Kaplan Medical Staff. USMLE Step 1 Lecture Notes 2017: 7-Book Set. Kaplan Publishing ; 2017