Bone marrow - nonneoplastic
Systemic disorders
Uncommon storage diseases


Topic Completed: 1 December 2006

Minor changes: 14 January 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed Search: Bone marrow storage diseases

Nat Pernick, M.D.
Page views in 2020 to date: 113
Cite this page: Pernick N. Uncommon storage diseases. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/bonemarrowuncommonstorage.html. Accessed May 26th, 2020.
Cystinosis
  • Nephrotic cystinosis is a rare autosomal disorder with defective cysteine transport out of lysosomes
  • Treated with cysteamine
  • Case report: 23 year old man with crystalline histiocytosis in hereditary cysinosis (Arch Pathol Lab Med 2002;126:1135)
  • Histology: crystals in marrow histiocytes and giant cells
  • Electron microscopy: various abnormal findings (J Clin Pathol 2005;58:939)
  • References: eMedicine: Cystinosis
Fabry disease
  • Also called alpha galactosidase A deficiency, angiokeratoma corporis diffusum universale
  • X linked (Xq22.1) recessive lysosomal storage disease that affects 1 per 40,000
  • Due to deficiency in lysosomal alpha galactosidase A, which catabolizes neutral glycosphingolipids
  • High penetrance in hemizygous males with symptoms at infancy or childhood
  • Heterozygous females have later age of presentation, more variable severity due to lyonization of X chromosome
    • May have normal leukocyte alpha galactosidase A activity
  • Deficiency causes intracellular accumulation of galabiosylceramide (ceramide trihexoside) and digalactosyl ceramide within skin, renal glomeruli and tubular epithelium, blood vessels, corneal epithelium, myocardium and ganglion cells
  • Frequently misdiagnosed
  • Case reports: 32 year old man with recurrent fevers of unknown origin (University of Pittsburgh: Recurrent Fevers of Unknown Origin); 32 year old man (Arch Pathol Lab Med 1980;104:17)
  • Treatment: recombinant human alpha galactosidase A replacement therapy has only a modest effect, perhaps due to heterogeneous distribution (Mol Genet Metab 2007;90:307)
  • Histology: cells with small globular, lightly eosinophilic inclusions
Mucopolysaccharidosis type VII
  • Very rare lysosomal storage disease due to deficiency of beta glucuronidase, which degrades glycosaminoglycans
  • Causes progressive accumulation of glycosaminoglycans and subsequent lysosomal distension in multiple tissues
  • Histology: Alder-Reilly granules in neutrophils, monocytes, basophils and eosinophils; cytoplasmic inclusions surrounded by clear vacuoles in lymphocytes, plasma cells, osteoblasts, macrophages
  • Positive stains: granulocytes, monocytes, lymphocytes - acid phosphatase
  • References: Am J Clin Pathol 1982;78:544, eMedicine: Genetics of Mucopolysaccharidosis Type VII, Wikipedia: Sly Syndrome
Microscopic (histologic) images

Images hosted on other servers :

Cystinosis:

Fig 1: bone marrow biopsy shows hypocellular marrow with numerous
macrophages containing hexagonal, tubular and rectangular cysteine crystals
Fig 2/3: crystals are birefringent using polarizing and first order compensator filters




Fabry disease:

Kidney: podocytes are diffusely distended by intracytoplasmic vacuoles; scattered foam cells in interstitium

Kidney: PAS shows podocytes with foamy cell change


Lymph nodes: reactive hyperplasia

Positive staining - disease
Electron microscopy description
  • Fabry disease:
    • Characteristic single membrane bound intracellular inclusions (myelin-like figures, zebra bodies) that are 0.1 to 10 microns in diameter
    • Round and lamellated with concentric electron dense layers
    • Found in endothelial and smooth muscle cells, myocardium, fibroblasts and glomerular epithelium, urine sediment (Arch Pathol Lab Med 1981;105:361)
Electron microscopy images

Images hosted on other servers - cystinosis:

Normal platelets

Platelets contain variable dense granules

Platelet undergoing spontaneous release

Differential diagnosis of foam cell change
  • Fucosidosis
  • Gangliosidoses
  • Gaucher disease
  • Mucopolysaccharidoses: all have different intracellular distribution and ultrastructural features of inclusions, can detect by laboratory assays
  • Treatment with chloroquine, amiodarone or aminoglycosides: have similar myelin-like figures (Hum Pathol 2003;34:285)
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