Niemann Pick Disease Flashcards
A 9-month-old girl is brought to the pediatrician due to concerns about progressive developmental delay. The parents report that she has become less interactive and is no longer reaching developmental milestones. On examination, she has hepatosplenomegaly, hypotonia, and a cherry-red spot on the macula. Laboratory studies show low sphingomyelinase activity in leukocytes. Which of the following is the most likely accumulated substrate in this condition?
A) Glucocerebroside
B) Sphingomyelin
C) GM2 ganglioside
D) Globotriaosylceramide
E) Phytanic acid
Answer: B) Sphingomyelin
Explanation: Niemann-Pick Disease (types A and B) is caused by a deficiency of sphingomyelinase, leading to the accumulation of sphingomyelin in lysosomes. Type A presents with progressive neurodegeneration, hepatosplenomegaly, hypotonia, and the characteristic cherry-red macula. Diagnosis is confirmed by enzyme assay showing low sphingomyelinase activity and genetic testing.
Incorrect Answers:
A) Glucocerebroside accumulates in Gaucher disease, which presents with hepatosplenomegaly, pancytopenia, and bone crises, without neurodegeneration or cherry-red spots.
C) GM2 ganglioside accumulates in Tay-Sachs disease, characterized by neurodegeneration and a cherry-red macula but without hepatosplenomegaly.
D) Globotriaosylceramide accumulates in Fabry disease, presenting with neuropathic pain, angiokeratomas, and renal or cardiac involvement.
E) Phytanic acid accumulates in Refsum disease, a disorder of peroxisomal metabolism, which presents with retinitis pigmentosa, ataxia, and ichthyosis.
What is the genetic inheritance pattern of Niemann-Pick Disease?
Autosomal recessive inheritance
What enzyme deficiency causes Niemann-Pick Disease types A and B?
Deficiency of sphingomyelinase
What is the accumulated substrate in Niemann-Pick Disease?
Accumulation of sphingomyelin in macrophages
What are the clinical features of Niemann-Pick Disease type A?
Failure to thrive, developmental delay, hepatosplenomegaly, cherry-red macula, progressive neurodegeneration.
loss of developmental milestones.
symptoms develop around 2 to 6 months.
How does Niemann-Pick Disease type B differ from type A?
Type B lacks central nervous system involvement and presents with hepatosplenomegaly and lung disease
What are the characteristic findings on physical examination in Niemann-Pick Disease?
Hepatosplenomegaly, cherry-red macula, hypotonia, areflexia, and neurologic regression (in type A)
What is the pathognomonic finding in the fundus in Niemann-Pick Disease?
Cherry-red macula
What is the characteristic histological finding in Niemann-Pick Disease?
Foam cells (lipid-laden macrophages)
How is Niemann-Pick Disease diagnosed?
Enzyme assay (low sphingomyelinase activity) and genetic testing
What is the primary management strategy for Niemann-Pick Disease?
Supportive care, as there is no specific treatment available; bone marrow transplantation is experimental
death usually results within a few years.
