Complex lipid accumulations: lipidosis
Lipidosis is a group of inherited metabolic disorders where harmful amounts of fats or lipids accumulate in the body’s cells. These are enzymopathies, where there is a failure to breakdown lipids. Tissue damage is classically seen in the brain, peripheral nervous system, liver, spleen and bone marrow.
There are two main classifications of lipidosis:
- Sphingolipidoses
- Related to sphingolipid metabolism
- Include Niemann-Pick disease, Fabry disease, Krabbe disease, Farber disease and others
- Other
- Non-sphingolipid related disorders
- Include fucosidosis, Schindler disease and Wolman disease
H&E, bone marrow in Gaucher disease: Gaucher cells – large macrophages with pale, finely striated ('crumpled tissue paper') cytoplasm and small eccentric nuclei; bone on the left.
Image: “Gaucher disease - very high mag” by Nephron, CC BY-SA 3.0, via Wikimedia Commons.
Examples: the classic sphingolipidoses:
- Gaucher (the commonest) – glucocerebrosidase: 'crumpled tissue paper' macrophages in spleen, liver and bone marrow.
- Niemann–Pick A/B – sphingomyelinase: foamy macrophages, hepatosplenomegaly; neurodegeneration in type A.
- Tay–Sachs – hexosaminidase A: GM2 ganglioside in neurons, cherry-red spot on the macula.
- Fabry – α-galactosidase A, X-linked: angiokeratomas, painful neuropathy, kidney and heart disease.
These can be autosomal recessive or X linked.
Lipidosis is considered part of a wider group of disorders known as lysosomal lipid storage diseases. Lysosomes, you’ll remember, are sacs of enzymes which digest large molecules and pass on the fragments for use, they are, in effect, the catabolic agent of lipids.
Diagnosis of lipidosis is done through clinical examination, biopsy, genetic testing, molecular analysis of cells or tissues and enzyme assays. There is no specific treatment, however we have a number of therapies for certain conditions to alleviate symptoms.