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Mucopolysaccharide storage disease type 1 (Hurler syndrome) (NORD)





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Mucopolysaccharide storage disease type 1 (Hurler syndrome) (NORD)
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Mucopolysaccharide storage disease type 1 (Hurler syndrome) (NORD)


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High Yield Notes
5 pages

Mucopolysaccharide storage disease type 1 (Hurler syndrome) (NORD)

8 flashcards

USMLE® Step 1 style questions USMLE

2 questions

A 3-year-old girl is brought to the clinic for evaluation of abnormal development and poor performance at school. The child is currently seeing an ophthalmologist for evaluation of poor vision. The parents state the child has had difficulty walking on her own over the past few months, and they have noted a curvature to her spine causing her to walk with a “hunched back.” The patient has a history of multiple sinus and respiratory infections over the past 2 years, requiring antibiotics for treatment. The family is part of an Amish community. Head circumference is above the 95th percentile. Facial features are notable for a prominent forehead, flat nose bridge and enlarged lips, gums, and tongue. Abdominal examination reveals hepatosplenomegaly and an umbilical hernia. Ophthalmic examination reveals corneal clouding. Fundoscopic examination reveals optic atrophy.  Which of the following is the most likely diagnosis?

External References

Content Reviewers:

Rishi Desai, MD, MPH

Mucopolysaccharidosis type I, or MPS I, is a rare genetic metabolic disorder caused by deficiency of a lysosomal enzyme required to break down mucopolysaccharides.

The disorder presents as a spectrum ranging from severe forms, classically known as Hurler syndrome, which are associated with life-threatening complications, to attenuated forms, classically known as Scheie syndrome or Hurler-Scheie syndrome.

This disease can cause significant disability but it can also have a near-normal life expectancy.

However, since presentation varies greatly between individuals, these designations are imprecise, so Hurler syndrome is generally used for severely affected individuals and attenuated mucopolysaccharidosis type I is used for all others.

Mucopolysaccharides, also known as glycosaminoglycans, are complex sugars produced by cells and exported to the extracellular space.

They include various molecules including heparan sulfate and dermatan sulfate, and they can be found on almost all cell surfaces as well as in the basement membrane, which separates epithelial cells from the connective tissue underneath.

Mucopolysaccharides are degraded inside the cell, where they’re engulfed by a lysosome, that releases enzymes, which breakdown mucopolysaccharides.

Each mucopolysaccharide requires multiple enzymes to fully degrade, and some mucopolysaccharides are degraded by the same enzymes.

For example, both heparan sulfate and dermatan sulfate need the lysosomal enzymes iduronate sulfatase and alpha-L-iduronidase to be broken down.

MPS I is an autosomal recessive disorder, caused by a variation in the IDUA gene, which results in alpha-L-iduronidase deficiency.

This deficiency prevents heparan sulfate and dermatan sulfate from being degraded, and as a result they build up in various tissues, leading to many complications as well as distinctive facial features, like a prominent forehead, a flat nose bridge, and enlarged lips, tongue, and gums.

MPS I is also classically associated with corneal clouding, where the corneas turns opaque, leading to visual problems and even blindness.

Skeletal malformations like short stature, kyphosis, hip dysplasia, and joint disease are also common, as well as other complications like hernias, respiratory problems, cardiomyopathy, thickened heart valves, hydrocephalus, and neurosensorial hearing loss.

The severe form also causes severe developmental delays and intellectual disability, which are not seen with the attenuated form.

Screening for MPS I can be done by testing the urine for mucopolysaccharides, and measuring alpha-L-iduronidase enzyme activity in leukocytes.

In the United States, the disorder was recently added to the Recommended Uniform Screening Panel.

The diagnosis can be confirmed through molecular genetic testing for newborns.


Mucopolysaccharide storage disease type 1 also known as Hurler syndrome, is an inherited disorder caused by a deficiency of the enzyme alpha-L-iduronidase. This enzyme is necessary for breaking down complex molecules called mucopolysaccharides.

When alpha-L-iduronidase is deficient, the mucopolysaccharides are not broken down properly, leading to a buildup of these molecules in the body's cells. This causes a wide range of symptoms, including physical abnormalities, cognitive disabilities, and corneal clouding. Treatment for this condition includes enzyme replacement therapy, bone marrow transplant, and physical and occupational therapy.