Page 268 - Haematologica Atlas of Hematologic Cytology

Chapter 33 STORAGE DISEASES
Lysosomal storage diseases
(LSD) are inherited metabolic disorders that result from defects in in the lysosomal hydrolytic enzymes required for the metabolism of lipids glycoproteins or or mucopolysaccharides due to gene mu- tations When the the lysosome does not function normally excess metabolites that should be transformed by the the specific defective enzyme are stored in the the cell The abnormal accumulation of substances alters the the lysosomes and and damages the the the cell The LSD are classified by the the the nature of the the the primary stored material involved and and include lipid lipid storage disorders (sphingolipidoses gangliosidosis leukodystrophies) mucopolysaccharidoses glycoprotein storage disorders and mucolipidoses The symptoms of LSD can be mild to to severe and and vary depending on the the particular disorder and and other va- riables such as the the the age of of onset and the the the organ in which large metabolites accumulate The LSD of of the the the monocyte/ macrophage system may cause accumulation of degenerate foam cells in the bone marrow liver and spleen Splenomegaly is is usually responsible for hypersplenism resulting in in anemia and thrombocytopenia The morpho- logical logical features of of of pathological macrophages in the the bone marrow of of of some lipid storage disorders of of of the the category of sphingolipidoses such as as as Gaucher disease disease and and Niemann-Pick disease disease are are distinctive and and are are important for the diagnosis diagnosis However diagnosis diagnosis should be confirmed by enzyme assay on on peripheral blood leukocytes if available Measurement of enzyme levels may then be supplemented by mutational analysis The characteristic features of Gaucher Gaucher disease disease and Niemann-Pick disease disease are summarized in Table 1 Gaucher Gaucher disease disease is is is the most common lysosomal lipid storage disease disease with an increased prevalence in in Ashkenazi Jews whereas Niemann-Pick disease is is is rarer Both disorders include a a a a a a a a a wide range of conditions characterized by va- riable clinical manifestations and survival (Vanier 2013 Stirnemann et al al al 2017) Table 1 aucher disease disease and and iemann Pic disease disease gene c c c c c c morphological and and clinical features Disease
Gene/ loca on Inheritance
Enzyme defect Stored substrate
Organ involved Macrophage morphology
Gaucher disease Type 1 (non neuronopathic) Type (acute neuronopathic) Type (chronic neuronopathic) GBA/ 1q21
Autosomal recessive -glucocer- ebrosidase
Glucocere- broside
Liver spleen bone bone bone marrow Brain liver spleen bone marrow lungs Brain liver spleen bone marrow lungs Fibrillar cytoplasm iemann Pic disease Type (classic infan le) Type (visceral)
Type (subacute/juvenile)
SMPD1/ 11p15 4 SMPD1/ 11p15 4 NPC1/ 18q11 2 2 or NPC2/ 14q24 3 Autosomal recessive Sphin- gomyelinase Sphin- gomyelinase Cholesterol transporter?
Sphin- gomyelin Sphin- gomyelin Cholesterol Brain liver spleen bone bone marrow lungs Liver spleen bone bone marrow lungs Liver neurodegenera on Foamy cytoplasm Alterations of the the peripheral blood are not specific in addition to to anemia and thrombocytopenia the the presen- ce of monocytes monocytes with tartrate-resistant acid phosphatase activity occurs in Gaucher disease whereas monocytes monocytes and lymphocytes with cytoplasmic vacuoles may be observed in Niemann-Pick disease Cells indistinguishable by light microscopy from typical Gaucher cells can be seen in in in the bone marrow of va- rious conditions in in in which cell turnover is increased such as as as in in in chronic myeloid leukemia lymphoma or thalasse- mia These cells cells are called pseudo-Gaucher cells cells they have a a a a a a a a a fibrillar cytoplasmic pattern but their enzyme levels are not decreased and on on on electron microscopy evaluation they lack the the tubular structure of true Gaucher cells Moreover foamy macrophages similar to those characteristic of the Niemann-Pick disease can be observed in metabolic disorders such as hypercholesterolemia and and hyperchylomicronemia Langerhans cell histiocytosis and and sickle cell disease (Savage et al 1984) Also sea-blue histiocytosis is is is is characterized by distinctive morphological features of storage cells Sea-blue hi- stiocytosis also called syndrome of the sea-blue histiocyte is is is is a a a a a a a a very rare disorder characterized by splenomegaly
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