Krabbe Disease Flashcards
A 6-month-old male infant is brought to the clinic due to progressive irritability, poor feeding, and developmental delay. The parents report that he has become more floppy over the past month. On examination, the infant exhibits hypotonia, hyperreflexia, and poor visual tracking. MRI of the brain shows marked demyelination of the white matter. Laboratory studies reveal low galactocerebrosidase activity in leukocytes.
Which of the following best explains the pathophysiology of this condition?
A) Accumulation of GM2 ganglioside in neurons
B) Accumulation of sphingomyelin in macrophages
C) Accumulation of galactocerebroside and psychosine, leading to oligodendrocyte toxicity
D) Accumulation of glucocerebroside in macrophages
E) Defective metabolism of very-long-chain fatty acids
Answer: Accumulation of galactocerebroside and psychosine, leading to oligodendrocyte toxicity
Explanation: Krabbe Disease is an autosomal recessive lysosomal storage disorder caused by a deficiency of galactocerebrosidase (GALC). This leads to the accumulation of galactocerebroside and psychosine, both of which are toxic to oligodendrocytes. The resulting loss of myelin and severe neurodegeneration manifest as developmental delay, hypotonia, and progressive neurologic decline. Histologically, globoid cells (multinucleated macrophages) are seen in the white matter.
Incorrect Answers:
A) Accumulation of GM2 ganglioside occurs in Tay-Sachs disease, which also presents with neurodegeneration but lacks hypotonia and has a cherry-red macula.
B) Accumulation of sphingomyelin occurs in Niemann-Pick disease, which presents with hepatosplenomegaly and a cherry-red macula.
D) Accumulation of glucocerebroside occurs in Gaucher disease, characterized by hepatosplenomegaly, bone pain, and pancytopenia without neurodegeneration.
E) Defective metabolism of very-long-chain fatty acids occurs in peroxisomal disorders such as Zellweger syndrome or adrenoleukodystrophy, not Krabbe disease.
What is Krabbe disease?
Krabbe disease is a rare, inherited disorder that affects the nervous system due to the deficiency of the enzyme galactocerebrosidase.
True or False: Krabbe disease is also known as globoid cell leukodystrophy.
True
What is the genetic inheritance pattern of Krabbe Disease?
Autosomal recessive inheritance
True or False: Krabbe disease affects both males and females equally.
True
What populations are at higher risk for Krabbe Disease?
Increased incidence in individuals of Scandinavian and Northern European descent.
True or False: Krabbe disease can be diagnosed through newborn screening.
True
What is the role of galactocerebrosidase in the body?
Galactocerebrosidase breaks down galactolipids in myelin.
What is the mechanism by which Krabbe disease affects the nervous system?
The lack of galactocerebrosidase leads to the buildup of toxic substances that damage myelin, impairing nerve function.
What enzyme deficiency causes Krabbe Disease?
Deficiency of galactocerebrosidase (GALC).
Fill in the blank:
The accumulation of __________ in Krabbe disease leads to damage in the myelin sheath.
Galactolipids.
What specific substrates accumulate in Krabbe Disease?
Accumulation of galactocerebroside and psychosine, which are toxic to oligodendrocytes
What is the primary pathological feature found in the brains of patients with Krabbe disease?
Demyelination of the white matter.
Multiple choice: What is the most common age for diagnosis of Krabbe disease? A) Newborns B) 1-3 years C) 3-6 months D) 6-12 years
C) 3-6 months
What feature is associated with the progressive neuropathy seen in Krabbe Disease?
Early symptoms are: hypotonia and areflexia.
Later symptoms are: spasticity, hypertonia, and opisthotonus.
Common symptoms include irritability, feeding difficulty, developmental delays, muscle stiffness, and seizures.
