Metachromatic Leukodystrophy Flashcards
A 4-year-old girl is brought to the clinic due to difficulty walking and frequent falls. Her parents report that she was previously developing normally but has become increasingly clumsy and confused over the past six months. On examination, she has ataxia, spasticity, and mild hypotonia. MRI of the brain shows symmetric white matter hyperintensities. Laboratory testing reveals decreased arylsulfatase A activity in leukocytes and elevated sulfatides in urine. Which of the following is the most likely pathophysiological mechanism underlying this condition?
A) Accumulation of galactocerebroside in oligodendrocytes
B) Accumulation of sulfatides due to defective degradation
C) Accumulation of GM2 ganglioside in neurons
D) Accumulation of sphingomyelin in macrophages
E) Accumulation of glucocerebroside in macrophages
Answer: B) Accumulation of sulfatides due to defective degradation
Explanation: Metachromatic Leukodystrophy is an autosomal recessive lysosomal storage disorder caused by a deficiency of arylsulfatase A, leading to the accumulation of sulfatides in the nervous system. Sulfatides are toxic to oligodendrocytes and Schwann cells, causing progressive demyelination. Symptoms include ataxia, spasticity, and cognitive decline. Diagnosis is confirmed by reduced arylsulfatase A activity and elevated sulfatides in urine or tissues.
Incorrect Answers:
A) Accumulation of galactocerebroside occurs in Krabbe disease, which presents with developmental delay, hypotonia, and irritability in infancy.
C) Accumulation of GM2 ganglioside occurs in Tay-Sachs disease, characterized by neurodegeneration and a cherry-red macula but without demyelination.
D) Accumulation of sphingomyelin occurs in Niemann-Pick disease, presenting with hepatosplenomegaly and neurodegeneration.
E) Accumulation of glucocerebroside occurs in Gaucher disease, presenting with hepatosplenomegaly, bone pain, and pancytopenia.
What is Metachromatic Leukodystrophy (MLD)?
MLD is a genetic disorder caused by the deficiency of the enzyme arylsulfatase A, leading to the accumulation of sulfatides and demyelination.
True or False: Metachromatic Leukodystrophy is an autosomal dominant disorder.
False, it is an autosomal recessive disorder.
True or False: Metachromatic Leukodystrophy can be detected in newborn screening programs.
True, it can be detected through newborn screening for lysosomal storage disorders.
True or False: Metachromatic Leukodystrophy is more common in males than females.
False, it affects both sexes equally.
What is the function of the ARSA gene?
The ARSA gene encodes the enzyme arylsulfatase A, which is involved in the breakdown of sulfatides.
What enzyme is deficient in Metachromatic Leukodystrophy?
Aryl-sulfatase A.
Fill in the blank: The accumulation of __________ in MLD leads to demyelination.
sulfatides
What is the significance of sulfatide accumulation in Metachromatic Leukodystrophy?
Sulfatide accumulation leads to the disruption of myelin formation and maintenance.
Fill in the blank: Metachromatic Leukodystrophy primarily affects the __________ system.
nervous
What is the most common form of Metachromatic Leukodystrophy?
The late-infantile form is the most common.
What are the common clinical manifestations of Metachromatic Leukodystrophy?
Symptoms include progressive neuropathy, motor dysfunction, ataxia, hypotonia, cognitive decline, and seizures.
At what age do symptoms of Metachromatic Leukodystrophy typically appear?
Symptoms can appear in childhood, typically between 1 and 2 years of age.
What is the classic presentation of late-onset Metachromatic Leukodystrophy?
Symptoms typically include progressive cognitive decline and gait disturbances starting in adolescence or adulthood.
What is a common neurological symptom of Metachromatic Leukodystrophy?
A common symptom is ataxia.
What is a key diagnostic tool for Metachromatic Leukodystrophy?
Magnetic Resonance Imaging (MRI) is a key diagnostic tool.
What is the primary imaging finding in patients with Metachromatic Leukodystrophy?
The primary finding is bilateral symmetric white matter changes on MRI.
