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.
What key clinical feature is seen in the early phases of Krabbe Disease?
Optic atrophy (pale optic nerve).
Multiple choice: Which of the following is a common complication of Krabbe disease? A) Diabetes B) Osteoporosis C) Seizures D) Hypertension
C) Seizures
Fill in the blank: Patients with Krabbe disease may exhibit __________ due to demyelination.
Ataxia.
What are the late complications of Krabbe Disease?
Blindness.
Deafness.
Severe neurologic decline leading to early death.
Multiple choice: Which of the following is NOT a symptom of Krabbe disease? A) Muscle weakness B) Hearing loss C) Vision impairment D) Frequent colds
D) Frequent colds
Which imaging technique is often used to diagnose Krabbe disease?
Magnetic resonance imaging (MRI).
How is the diagnosis of Krabbe Disease confirmed?
Enzyme activity assay showing low galactocerebrosidase activity; genetic testing
Fill in the blank:
__________ testing can confirm a diagnosis of Krabbe disease by measuring galactocerebrosidase activity.
Enzymatic
What is the characteristic histological finding in Krabbe Disease?
Globoid cells (multinucleated macrophages) in the white matter.
Not of diagnostic value, but seen at autopsy.
True or False: There is a cure for Krabbe disease.
False
What is the primary treatment for Krabbe Disease?
Hematopoietic stem cell transplantation (HSCT) may slow progression if initiated early; otherwise, supportive care
Is gene therapy currently a viable treatment option for Krabbe disease?
No, gene therapy is still under research and not yet a viable treatment option.
What is the primary focus of supportive care in patients with Krabbe disease?
To manage symptoms and improve quality of life.
What are the treatment options available for Krabbe disease?
Treatment options are limited and may include supportive care, physical therapy, and in some cases, hematopoietic stem cell transplantation.
At what age do symptoms of Krabbe disease typically begin to appear?
Symptoms usually appear in infancy, typically between 3 to 6 months of age.
What is the typical prognosis for children diagnosed with Krabbe disease?
The prognosis is generally poor, with many children not surviving past early childhood and death typically occurring by age 2 in infantile form.
