Pathophysiology
1) lipid storage disease with accumulation of cholesterol and sphingomyelin in tissues 2) cause is defect in sphingomyelinase 3) type A – has neurological disease and onset within the first 6 months of birth 4) type B – absence of neurologic disease and onset in childhood
Signs and Symptoms
1) hepatomegaly 2) progressive neurologic disease (type A) 3) seizures 4) central cherry red spot on funduscopy 5) macular degeneration 6) mental retardation 7) pulmonary/respiratory failure (type B)
Characteristic Test Findings
Laboratory – 1) increased LDLs Radiology – 2) reticular pattern in lung fields on chest radiograph with type B
Histology/Gross Pathology
1) sphingomyelin and cholesterol accumulate in lysosomes of macrophages, forming large foamy cells in liver, lymph nodes, spleen, and lungs 2) shrunken gyri and widened sulci with diffuse vacuolization of neurons
Associated Conditions
1) pulmonary hypertension 2) cor pulmonale 3) bronchopneumonia
Biochemistry
mutation in NPC1 gene (gene encodes for a protein that acts in cholesterol transport from lysosome to ACAT)
Inheritance/Epidemiology
1) autosomal recessive 2) death is often at 10-20 years
Treatment
1) enzyme replacement trials are underway 2) hematopoietic stem cell gene therapy trials are underway 3) bone marrow transplantation has been successful in a limited number of patients 4) whole-lung lavage improves lung functioning
Tips for USMLE
1) central cherry red spot on funduscopy is also seen in Tay Sachy and central retinal artery occlusion 2) Niemann-Pick type C results from defective cholesterol transport across lysosomal membranes 3) if the question mentions foam cells, think Niemann Pick
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