USMLE Step 1 · Biochemistry & Genetics

Hurler syndrome vs Hunter syndrome

How to tell Hurler syndrome and Hunter syndrome apart when a board question makes them look alike.

Fastest separator

Hurler has corneal clouding; Hunter has no corneal clouding and is X-linked with iduronate sulfatase deficiency.

Side by side

Hurler syndromeHunter syndrome

Key clue

Hurler syndrome causes coarse facies, corneal clouding, hepatosplenomegaly, skeletal abnormalities, developmental delay, and increased dermatan and heparan sulfate.

Hunter syndrome causes coarse facies, aggressive behavior, hepatosplenomegaly, airway disease, skeletal abnormalities, and no corneal clouding, with X-linked inheritance.

Mechanism

Alpha-L-iduronidase deficiency prevents degradation of dermatan and heparan sulfate.

Iduronate sulfatase deficiency causes glycosaminoglycan accumulation and is classically X-linked recessive.

Labs and tests

Corneal clouding and alpha-L-iduronidase deficiency support Hurler syndrome.

No corneal clouding, X-linked male patient, and iduronate sulfatase deficiency support Hunter syndrome.

The trap

Both are mucopolysaccharidoses with coarse facies and organomegaly; the eye finding and inheritance are the fast split.

Watch it explained

60-second lessonHurler vs Hunter Syndrome: The Cornea Trick That Always Works (USMLE Step 1)

Quiz yourselfHurler or Hunter? 6-Second Biochem Pop Quiz (USMLE Step 1)

Test it now

The repair move

For coarse facies plus organomegaly plus developmental regression in a child, walk the mucopolysaccharidosis algorithm: (1) check inheritance pattern (a boy only with X-linked recessive pattern points Hunter syndrome from iduronate sulfatase deficiency; both sexes affected with autosomal recessive pattern points Hurler syndrome from alpha-L-iduronidase deficiency); (2) check the cornea (clear corneas point Hunter; cloudy corneas with gargoylism point Hurler); (3) confirm with enzyme assay or genetic testing, then offer enzyme replacement therapy (laronidase for Hurler, idursulfase for Hunter) or hematopoietic stem cell transplant; early intervention before age 2 gives the best neurologic outcome.

Try a free question

Core

A 2-year-old boy has coarse facial features, prominent forehead, hepatosplenomegaly, joint stiffness, developmental delay, and clouding of the corneas on slit-lamp examination. Urine shows elevated dermatan and heparan sulfate. Family history is unremarkable. Which enzyme deficiency is most likely?

Show answer and explanation

Answer: A. Alpha-L-iduronidase (Hurler syndrome). Hurler syndrome (MPS I) is autosomal recessive alpha-L-iduronidase deficiency causing dermatan and heparan sulfate accumulation; the classic clue is CORNEAL CLOUDING with coarse facies, hepatosplenomegaly, developmental delay, and joint stiffness.

Why the other choices are tempting

B. Iduronate sulfatase deficiency (Hunter syndrome) is X-linked and has NO corneal clouding.
C. N-acetylgalactosamine-6-sulfatase deficiency (Morquio) causes skeletal dysplasia with preserved intelligence.
D. Beta-galactosidase deficiency causes GM1 gangliosidosis with neurodegeneration, not the MPS phenotype here.
E. Heparan-N-sulfatase deficiency (Sanfilippo) emphasizes severe behavioral/CNS disease with milder somatic features.

Flashcards

Tap a card to flip it.

What clue supports Hurler syndrome?

Choose Hurler syndrome when the stem gives this pattern: Hurler syndrome causes coarse facies, corneal clouding, hepatosplenomegaly, skeletal abnormalities, developmental delay, and increased dermatan and heparan sulfate.

What clue supports Hunter syndrome?

Choose Hunter syndrome when the stem gives this contrasting pattern: Hunter syndrome causes coarse facies, aggressive behavior, hepatosplenomegaly, airway disease, skeletal abnormalities, and no corneal clouding, with X-linked inheritance.

Quick answers

What is the fastest way to tell Hurler syndrome from Hunter syndrome?