Question

A child with coarse facial features and developmental delay is found to have a deficiency of $\alpha$-L-iduronidase on enzyme testing. Which substances are expected to accumulate in this disorder?

• A. Dermatan sulfate + Chondroitin sulfate
• B. Only Dermatan sulfate
• C. Dermatan sulfate + Heparan sulfate
• D. Heparan sulfate + Chondroitin sulfate

Hint:

Hurler syndrome = $\alpha$-L-iduronidase deficiency = accumulation of dermatan sulfate and heparan sulfate.

Answer 1

The Correct Option is C

Step 1: Understanding the Question:
A deficiency of $\alpha$-L-iduronidase is the hallmark of Hurler syndrome (MPS I), a type of Mucopolysaccharidosis. The question asks for the specific glycosaminoglycans (GAGs) that build up as a result.
Step 2: Detailed Explanation:

Hurler Syndrome (MPS IH): This is an autosomal recessive lysosomal storage disorder. The defective enzyme, $\alpha$-L-iduronidase, is required for the degradation of specific GAGs (previously called mucopolysaccharides).

Accumulated Substances: The GAGs that cannot be broken down are Dermatan sulfate and Heparan sulfate. These accumulate in lysosomes across multiple tissues, including the heart, liver, bone, and brain.

Clinical Findings: Accumulation leads to "coarse" facial features (gargoylism), corneal clouding, hepatosplenomegaly, heart valve disease, and skeletal deformities (dysostosis multiplex). Developmental delay is common in the severe (Hurler) form.

Hunter Syndrome Comparison: Hunter syndrome (MPS II) also involves accumulation of dermatan and heparan sulfate, but it is caused by iduronate-2-sulfatase deficiency, is X-linked recessive, and notably lacks corneal clouding.

Laboratory Markers: The presence of dermatan and heparan sulfate in the urine is a key screening test for both MPS I and MPS II.

Step 3: Final Answer:
Deficiency of $\alpha$-L-iduronidase results in the systematic accumulation of Dermatan sulfate and Heparan sulfate.