Lysosomal storage diseases


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 of lysosomal storage diseases
Disease Inheritance Pathophysiology Clinical features Diagnostic findings

Gaucher disease

Krabbe disease

  • Galactocerebrosidase ↑ galactocerebroside and psychosine

Tay-Sachs disease

Fabry disease

  • α-Galactosidase Aceramide trihexoside
Metachromatic leukodystrophy
  • Arylsulfatase A ↑ cerebroside sulfate
  • -
Niemann-Pick disease
Hurler syndrome
  • Corneal clouding
Hunter syndrome
  • Aggressive behavior
I-cell disease
  • Coarse facial features
  • Corneal clouding
  • Gingival hyperplasia
  • Claw hand deformity
  • Kyphoscoliosis
  • -
  • -


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:

  • Sphingomyelin: derived from a ceramide with phosphorylcholine as a hydrophilic group
  • Cerebrosides: derived from a ceramide with a single sugar residue (galactose or glucose)
  • Gangliosides: derived from a ceramide with an oligosaccharide chain and one or more sialic acids linked to the chain

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

  • Etiology: autosomal recessive inherited disease [4]
  • Pathophysiology: lack of or reduced activity of the lysosomal enzyme galactocerebrosidase (GALC; also called galactosylceramidase) → accumulation of galactocerebroside and psychosine (toxic myelin degradation products) and formation of globoid cells demyelination and destruction of oligodendrocytes up to decerebration
  • Clinical features
  • Diagnostics: globoid cell (a large multinucleated cell of mesodermal origin that is found clustered in the brain tissue )
  • Treatment
    • Before symptom onset, stem cell transplantation may improve outcome.
    • Only supportive treatment is possible after symptom onset.

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

  • Etiology: X-linked recessive inherited disease [7]
  • Epidemiology
    • Typical onset is during childhood but may also appear in 60–80-year-old adults
    • Mainly affects boys
  • Pathophysiology: α-Galactosidase A deficiency → accumulation of ceramide trihexoside (also known as globotriaosylceramide) in the endothelium of vessels, in the epithelium of many organs, and in smooth muscle cells disorder affecting many organ systems
  • Clinical features
  • Treatment: enzyme replacement therapy with α-galactosidase A

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 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)
  • Deficiency of α-L-iduronidase
  • Deficiency of iduronate-2-sulfatase
Clinical features
  • Occur in both conditions (typically milder in Hunter syndrome):
    • Developmental delay
    • Facial dysmorphism: frontal bossing, elongated skull , flattened nasal bridge, broad nasal tip, thickened gingiva, anteverted nostrils, constant nasal discharge, spaced and protruded eyes.
    • Airway obstruction
    • Hepatosplenomegaly

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).


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

  • 1. Pastores GM, Hughes DA, Adam MP, et al. Gaucher Disease. url: Accessed January 24, 2018.
  • 2. 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): pp. 1463–9. doi: 10.1001/archinternmed.2010.302.
  • 3. 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): pp. 110–122. doi: 10.1016/j.ymgme.2014.11.008.
  • 4. Genetics Home Reference. Krabbe disease. Updated January 23, 2018. Accessed January 24, 2018.
  • 5. Kaback MM, Desnick RJ, Adam MP, et al. Hexosaminidase A Deficiency. url: Accessed January 24, 2018.
  • 6. Gross SJ, Pletcher BA, Monaghan KG, Professional Practice and Guidelines Committee. Carrier screening in individuals of Ashkenazi Jewish descent. Genet Med. 2008; 10(1): pp. 54–6. doi: 10.1097/GIM.0b013e31815f247c.
  • 7. Mehta A, Hughes DA, Adam MP, et al. Fabry Disease. url: Accessed January 24, 2018.
  • 8. Gomez-Ospina N, Adam MP, Ardinger HH, et al. Arylsulfatase A Deficiency. url: Accessed January 24, 2018.
  • 9. Wasserstein MP, Schuchman EH, Adam MP, et al. Acid Sphingomyelinase Deficiency. url: Accessed January 24, 2018.
  • 10. Patterson M, Adam MP, Ardinger HH, et al. Niemann-Pick Disease Type C. url: Accessed January 24, 2018.
  • 11. 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): pp. 3748–52. doi: 10.1073/pnas.88.9.3748.
  • 12. Schuchman EH, Desnick RJ. Types A and B Niemann-Pick disease. Mol Genet Metab. 2016; 120(1-2): pp. 27–33. doi: 10.1016/j.ymgme.2016.12.008.
  • 13. Kliegman R, Stanton B, St. Geme J, Schor N. Nelson Textbook of Pediatrics. Elsevier; 2015.
  • 14. White KK. Orthopaedic aspects of mucopolysaccharidoses. Rheumatology (Oxford). 2011; 50(Suppl 5): pp. v26–v33. doi: 10.1093/rheumatology/ker393.
  • 15. Matalon R, Matalon KM. The Mucolipidoses. Elsevier; 2015: pp. 365–368.
  • 16. 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): pp. 38–48. doi: 10.1136/jmg.2009.067736.
  • Le T, Bhushan V, Sochat M, Chavda Y. First Aid for the USMLE Step 1 2017. McGraw-Hill Education; 2017.
  • Kaplan Medical Staff. USMLE Step 1 Lecture Notes 2017: 7-Book Set. Kaplan Publishing; 2017.
last updated 11/12/2020
{{uncollapseSections(['VqcGxW0', 'Tqc6BW0', '2qcTBW0', 'gqcFBW0', 'F-cg_U0', '8-cO_U0', 'u-cp_U0', 'E-c8_U0', 'v-cA_U0', 'eqcxxW0', 'D-c1zU0', 'fqckBW0'])}}