Mucopolysaccharidoses
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Direct answer
Mucopolysaccharidoses are lysosomal storage disorders caused by deficiency of the enzymes that degrade glycosaminoglycans, so dermatan sulphate, heparan sulphate or keratan sulphate accumulate. Hurler, Hunter and Morquio syndromes are the most tested types, with coarse features, skeletal dysplasia and organomegaly in varying combinations. Each has a distinct enzyme and urinary GAG pattern, and urine screening followed by enzyme assay confirms the diagnosis.
What you must remember
- Hurler syndrome (MPS I): alpha-L-iduronidase deficiency, with corneal clouding, gibbus, coarse facies, hepatosplenomegaly, hernias and developmental delay.
- Hunter syndrome (MPS II): iduronate-2-sulphatase deficiency, X-linked recessive, with coarse features and claw hand, but no corneal clouding.
- Morquio syndrome (MPS IV): keratan sulphate accumulation, with short-trunk dwarfism, odontoid hypoplasia and corneal clouding, while intelligence is usually preserved.
- Sanfilippo syndrome (MPS III): heparan sulphate storage with marked neurodegeneration and only mild somatic features.
- Urinary GAG pattern: dermatan and heparan sulphate in Hurler and Hunter syndromes, and keratan sulphate in Morquio syndrome.
- Atlantoaxial risk: odontoid hypoplasia in Morquio syndrome predisposes to instability, which needs cervical assessment before anaesthesia.
- Treatment: haematopoietic stem cell transplantation, ideally early in Hurler syndrome, and enzyme replacement such as laronidase or idursulfase for somatic disease.
Matching the syndrome to the urinary GAG pattern
Urinary GAG analysis sorts most cases before the enzyme assay returns. The table sets the common syndromes side by side, and the distinguishing feature is the one examiners ask about.
| Syndrome | Enzyme defect | Urinary GAG | Distinguishing feature |
|---|---|---|---|
| Hurler (MPS I) | Alpha-L-iduronidase | Dermatan and heparan sulphate | Corneal clouding, gibbus |
| Hunter (MPS II) | Iduronate-2-sulphatase | Dermatan and heparan sulphate | Claw hand, no corneal clouding |
| Morquio (MPS IV) | N-acetylgalactosamine-6-sulphatase or beta-galactosidase | Keratan sulphate | Short trunk, normal intelligence |
| Sanfilippo (MPS III) | Several heparan sulphate enzymes | Heparan sulphate | Neurodegeneration, mild somatic signs |
Hurler and Hunter syndromes share a similar GAG pattern, so the presence or absence of corneal clouding and the behaviour profile separate them. Morquio syndrome stands apart because keratan sulphate is excreted and the intelligence is usually spared. Sanfilippo syndrome is the neurodegenerative type, and its somatic features are subtle compared with the other three, so behaviour change and developmental regression lead the history.
Where the exam tests mucopolysaccharidoses
Examiners test the GAG pattern, the sign that separates each syndrome and the safety issue of cervical instability. These traps recur.
- Trap: expecting intellectual disability in Morquio syndrome. Correct: intelligence is usually preserved, whereas odontoid hypoplasia and atlantoaxial instability are the dangerous features needing cervical imaging.
- Trap: expecting corneal clouding in Hunter syndrome. Correct: corneal clouding is typical of Hurler and Morquio syndromes, and Hunter syndrome usually spares the cornea.
- Trap: choosing heparan sulphate as the urinary GAG for Morquio syndrome. Correct: Morquio syndrome excretes keratan sulphate, the pattern that sets it apart from Hurler and Hunter.
Frequently asked questions
Which mucopolysaccharidosis has no corneal clouding?
Hunter syndrome, MPS II, usually lacks corneal clouding, though it causes coarse facies, hepatosplenomegaly and claw hand. It is X-linked recessive and caused by iduronate-2-sulphatase deficiency.
What is the urinary GAG pattern in Morquio syndrome?
Morquio syndrome, MPS IV, excretes keratan sulphate in urine, in contrast to dermatan and heparan sulphate in Hurler and Hunter syndromes. Quantitative urinary GAG analysis with this pattern guides the choice of enzyme assay.
Why is atlantoaxial instability important in Morquio syndrome?
Odontoid hypoplasia in Morquio syndrome predisposes to atlantoaxial instability, which can compress the spinal cord. Cervical spine assessment is therefore needed before anaesthesia or intubation in these children.
Does enzyme replacement therapy treat brain involvement in mucopolysaccharidosis?
Enzyme replacement therapy improves somatic features such as hepatosplenomegaly and mobility, but it does not cross the blood brain barrier well. Haematopoietic stem cell transplantation is used in Hurler syndrome partly to address neurological decline when given early.