Wolman disease

Definition: Wolman’s disease is a rare autosomal recessive lysosomal storage disease.

Synopsis

 failing to thrive
 progressive hepatosplenomegaly
 abdominal calcifications
 Peripheral blood: vacuolated lymphocytes
 Bone marrow aspiration: foamy histiocytes.
 adrenals ( adrenal Wolman disease )
 Liver ( hepatic Wolman disease )

• macroscopy: markedly enlarged, orange or butter-yellow with smooth and soft texture
• marked steatosis
• elliptical empty clefs predominantly in the Kupffer cells (cholesterol storage in the reticulo-endothelial cells)
• foamy histiocytes in portal tracts and periportal areas
• enlarged and vacuolated Kupffer cells
• portal fibrosis and periportal fibrosis
• lobular clusters of foamy macrophages
• polarisation: massive storage of birefringent material

 esophageal varices

 Intestine

• intestinal infiltration

 Spleen (splenic Wolman disease)
 Lymph nodes
 Bone marrow, thymus, tonsils, blood
 kidneys
 thyroid

 atherosclerosis

• early fatty streaks

  pulmonary hypertension
 diffuse punctate adrenal calcification
 acid cholesteryl ester hydrolase deficiency
 disseminated organ foam cell infiltration

• bone marrow foam cells
• vacuolated blood lymphocytes
• liver, adrenal, spleen, lymph nodes, bone marrow, small intestine, lungs and thymus, skin, retina, central nervous system

Ultrastructure

 large lipid droplets in enlarged lysosomes
 dilated and distended endoplasmic reticulum

Laboratory

 deficient acid lipase activity in the leukocytes and fibroblasts (by 4-methylumbelliferyl palmitate assay)

Etiology

 mutations in the lysosomal acid lipase (LIPA) gene at 10q24-q25

See also

 lysosomal acid lipase deficiency

• cholesteryl ester storage disease (CESD)