Bone marrow nonneoplastic
Storage-type histiocytosis
Niemann-Pick disease
Author: Nat Pernick, M.D.
Last author update: 1 December 2006
Last staff update: 16 June 2021
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: Bone marrow Niemann-Pick disease
Table of Contents
Definition / general | Treatment | Microscopic (histologic) description | Positive stains | Negative stains | Differential diagnosis | Additional references | Type A | Type B | Type C | Type DCite this page: Pernick N. Niemann-Pick disease. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonemarrowniemann.html. Accessed November 27th, 2024.
Definition / general
- Autosomal recessive sphingomyelin cholesterol lipidoses
- Types A / B: deficiency of lysosomal acid sphingomyelinase causes accumulation of sphingomyelin and other lipids in macrophages throughout the body
Treatment
- Bone marrow transplantation (variable improvement) (J Inherit Metab Dis 2003;26:775)
Microscopic (histologic) description
- Clusters and individual foam cells up to 90 microns
- Cytoplasm has clear vacuoles of varying size, may be mulberry or soap bubble-like
- Nuclei are small and round with coarse chromatin
Positive stains
Negative stains
Differential diagnosis
- Similar foam cells in hypercholesterolemia and Tangier disease
- Also disorders with massive cell destruction that overloads body's capacity to digest lipids (thalassemia, sickle cell anemia, ITP, chronic renal failure)
Additional references
Type A
Definition / general:
- Acute neuronopathic form
- Most common type
- Occurs in infants
- Presents with jaundice, hepatomegaly and profound brain damage
- Usually death by age 2 years
- No effective treatment
Molecular description:
- Types A and B due to mutations in SMPD1 gene
Additional references:
Type B
Definition / general:
- Chronic form (visceral form) without nervous system involvement
- Highest incidence in those of Turkish, Arabic and North African descent
- Uncommon in Ashkenazi Jews (Am J Hum Genet 2002;71:1413)
- Onset of hepatosplenomegaly in preteen years
- Good prognosis
- May eventually require oxygen therapy due to lung involvement
Treatment:
- Bone marrow transplantation
- Enzyme replacement
Micro description:
- Large macrophages with foamy cytoplasm
- Also sea blue histiocytes (Ann Hematol 2001;80:620)
Molecular description:
- Types A and B due to mutations in SMPD1 gene
Additional references:
Type C
Definition / general:
- Chronic neuronopathic form (NPC)
- Rare (1 per 100K live births) disease of newborns
- Autosomal recessive
- May present in first few months of life with cholestatic jaundice or hepatosplenomegaly or develop in adult years
- Fatal in some; others live into adulthood
- 95% have mutations of NPC1 gene
- Involves error of trafficking of cholesterol leading to accumulation of unesterified cholesterol, not sphingomyelin
Micro description:
- Macrophages with abnormal cholesterol storage (foam cells) in 60% (Arch Dis Child 2006;91:841)
- May also have sea blue histiocytes
Micro images:
Images hosted on other servers:
Foamy cells
Molecular description:
- Due to mutations in NPC1 (OMIM: NPC1 Gene; NPC1) or NPC2 (OMIM: NPC2 Gene; NPC2) genes
Additional references:
Type D
Definition / general:
- Variable age of presentation
- May have extensive brain damage
- Usually moderate hepatosplenomegaly
- Involves error of trafficking of cholesterol leading to accumulation of unesterified cholesterol, not sphingomyelin
- Associated with family origin in Nova Scotia, Canada
