Hurler Syndrome

Question 1

A 2-year-old boy is brought to the pediatrician due to developmental delay and coarse facial features. His parents report progressive worsening of his ability to walk and increasing joint stiffness. On examination, the child has hepatosplenomegaly, corneal clouding, and a hoarse voice. Laboratory studies reveal elevated levels of dermatan sulfate and heparan sulfate in the urine. Which of the following is the most likely underlying enzyme deficiency?

A) α-L-iduronidase
B) Iduronate-2-sulfatase
C) Arylsulfatase A
D) Glucocerebrosidase
E) Galactocerebrosidase

Answer 1

Answer: A) α-L-iduronidase

Explanation: Hurler Syndrome (Mucopolysaccharidosis type I) is an autosomal recessive lysosomal storage disorder caused by a deficiency of α-L-iduronidase, leading to the accumulation of dermatan sulfate and heparan sulfate. Clinical features include coarse facial features, hepatosplenomegaly, corneal clouding, developmental delay, and skeletal abnormalities. Early recognition and enzyme replacement therapy can improve outcomes.

Incorrect Answers:

B) Iduronate-2-sulfatase deficiency causes Hunter Syndrome, which shares similar features but lacks corneal clouding.
C) Arylsulfatase A deficiency causes metachromatic leukodystrophy, characterized by progressive demyelination and neurologic decline.
D) Glucocerebrosidase deficiency causes Gaucher disease, presenting with hepatosplenomegaly and pancytopenia.
E) Galactocerebrosidase deficiency causes Krabbe disease, associated with irritability and severe neurodegeneration in infancy.

Question 2

What is Hurler Syndrome?

Answer 2

A genetic disorder caused by the deficiency of the enzyme alpha-L-iduronidase, leading to accumulation of glycosaminoglycans.

Question 3

True or False: Hurler Syndrome is also known as Mucopolysaccharidosis Type I (MPS I).

Answer 3

True.

Question 4

What is the inheritance pattern of Hurler Syndrome?

Answer 4

Autosomal recessive.

Question 5

What genetic mutation is commonly associated with Hurler Syndrome?

Answer 5

Mutations in the IDUA gene.

Question 6

Which enzyme is deficient in Hurler Syndrome?

Answer 6

Alpha-L-iduronidase.

Question 7

True or False: Hurler Syndrome can be diagnosed using newborn screening.

Answer 7

True.

Question 8

True or False: Hurler Syndrome is more prevalent in males than females.

Answer 8

False; it affects both genders equally.

Question 9

What is a typical age of onset for symptoms of Hurler Syndrome?

Answer 9

Symptoms usually appear between 6 months to 2 years of age.

Question 10

What are common clinical features of Hurler Syndrome?

Answer 10

• Coarse facial features, “Gargoylism.”
• Corneal clouding
• Skeletal abnormalities (Dysostosis multiplex)
• Developmental delays
• Hepatosplenomegaly
• Cardiac issues
• inguinal and umbilical herniations

Question 11

What is the significance of the corneal clouding in Hurler Syndrome?

Answer 11

It is a characteristic finding and can lead to vision impairment.

A mnemonic to help distinguish Hurler from Hunter:
“Hurler can’t HUNT because of opacified corneas”
-Hurler syndrome has corneal clouding
-Hunter lacks corneal clouding

Question 12

Fill in the blank: Affected individuals of Hurler Syndrome often have __________ hearing loss.

Answer 12

Conductive.

Question 13

What are the neurological implications of Hurler Syndrome?

Answer 13

Progressive cognitive decline and behavioral issues.

Question 14

What is a common psychological impact on children with Hurler Syndrome?

Answer 14

Autism spectrum disorders.

Behavioral issues.

Question 15

Fill in the blank: Patients with Hurler Syndrome often exhibit __________ growth.

Answer 15

Dwarfism.

Question 16

What is the hallmark urinary finding in Hurler Syndrome?

Answer 16

Increased levels of urinary glycosaminoglycans (dermatan sulfate and heparan sulfate).

Question 17

True or False: Enzyme replacement therapy is available for Hurler Syndrome.

Answer 17

True.

Question 18

What is the name of the enzyme replacement therapy used for Hurler Syndrome?

Answer 18

Laronidase.

Question 19

What imaging study is typically used to evaluate skeletal abnormalities due to dysostosis multiplex seen in Hurler Syndrome?

Answer 19

X-rays.

Dysostosis multiplex is a rare disease of congenital origin characterized by chondrodystrophic skeletal changes and deposition of a lipid-like substance in many of the body tissues. The typical picture is that of dwarfism with deformity of the limbs and enlargement of the liver and spleen.

Question 20

Fill in the blank: Hurler Syndrome patients may develop __________ heart disease.

Answer 20

Valvular.

Question 21

What is the most common cause of death in patients with Hurler Syndrome?

Answer 21

Respiratory infections or cardiac complications.

Question 22

What is the role of supportive care in managing Hurler Syndrome?

Answer 22

To address developmental, physical, and psychological needs of the patient.

One significant supportive measure is addressing these patient’s obstructive sleep apnea with polysomnography.

Question 23

What is the prognosis for untreated Hurler Syndrome?

Answer 23

Significantly reduced life expectancy, often leading to death in childhood or early adulthood.

Question 24

What is the typical lifespan of individuals with untreated Hurler Syndrome?

Answer 24

Around 10 years.

Question 25

What is the role of hematopoietic stem cell transplantation in Hurler Syndrome?

Answer 25

It can provide a source of the deficient enzyme and improve outcomes if performed early.