AssessmentsNiemann-Pick disease types A and B (NORD)
Niemann-Pick disease types A and B (NORD)
USMLE® Step 1 style questions USMLE
A 10-month-old boy and his mother present to a pediatrics clinic due to the abrupt onset of seizures and general spasticity in the infant. Physical examination of the patient reveals decreased visual acuity bilaterally as well as hepatosplenomegaly. Fundoscopic exam reveals macular degeneration in both eyes. Biopsy of the brain, liver, or bone marrow in this patient would likely show histiocytic lysosomes (foam cells) filled with sphingomyelin.
Which of the following is the most likely diagnosis for this patient?
Content Reviewers:Rishi Desai, MD, MPH
Niemann-Pick disease type A and type B, or NPD-A and NPD-B, which are subtypes of acid sphingomyelinase or ASM deficiency, are rare, genetically inherited conditions characterized by the inability to break down a fat called sphingomyelin due to a deficiency of the enzyme, acid sphingomyelinase.
There’s also Niemann-Pick disease type C, which is known to be caused by mutations in the genes NPC1 and NPC2, and is therefore considered to be distinct from types A and B.
Sphingomyelin is a fat that's included in the membrane of many different cells.
They contain organelles called lysosomes that are said to function as recycling centers because they break down large, potentially harmful substances to be reused by the body.
They break down sphingomyelin by using an enzyme called acid sphingomyelinase, which is a product of the sphingomyelin phosphodiesterase 1, or SMPD1 gene.
In Niemann-Pick disease types A and B, there’s a mutation in the SMPD1 gene that causes a defect in the production of sphingomyelinase, leading to an inability to break down sphingomyelin.
In NPD-A there’s almost a complete absence of sphingomyelinase activity, while NPD-B has some residual sphingomyelinase activity remaining.
The macrophages develop a characteristic lipid-laden appearance under microscopes and are called “foam cells.”
Sphingomyelin can also build up in other cell types in the body, reflecting impaired intracellular recycling of membranes and damaged organelles in lysosomes due to sphingomyelinase deficiency.
Signs and symptoms of NPD-A present early in life, and are usually life-threatening.