Skip to content

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





Population genetics
Genetic disorders
Down syndrome (Trisomy 21)
Edwards syndrome (Trisomy 18)
Patau syndrome (Trisomy 13)
Fragile X syndrome
Huntington disease
Myotonic dystrophy
Friedreich ataxia
Turner syndrome
Klinefelter syndrome
Prader-Willi syndrome
Angelman syndrome
Beckwith-Wiedemann syndrome
Cri du chat syndrome
Williams syndrome
Alagille syndrome (NORD)
Polycystic kidney disease
Familial adenomatous polyposis
Familial hypercholesterolemia
Hereditary spherocytosis
Huntington disease
Li-Fraumeni syndrome
Marfan syndrome
Multiple endocrine neoplasia
Myotonic dystrophy
Tuberous sclerosis
von Hippel-Lindau disease
Polycystic kidney disease
Cystic fibrosis
Friedreich ataxia
Gaucher disease (NORD)
Glycogen storage disease type I
Glycogen storage disease type II (NORD)
Glycogen storage disease type III
Glycogen storage disease type IV
Glycogen storage disease type V
Mucopolysaccharide storage disease type 1 (Hurler syndrome) (NORD)
Krabbe disease
Niemann-Pick disease types A and B (NORD)
Niemann-Pick disease type C
Primary ciliary dyskinesia
Phenylketonuria (NORD)
Sickle cell disease (NORD)
Tay-Sachs disease (NORD)
Wilson disease
Fragile X syndrome
Alport syndrome
X-linked agammaglobulinemia
Fabry disease (NORD)
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Mucopolysaccharide storage disease type 2 (Hunter syndrome) (NORD)
Lesch-Nyhan syndrome
Muscular dystrophy
Ornithine transcarbamylase deficiency
Wiskott-Aldrich syndrome
Mitochondrial myopathy
Autosomal trisomies: Pathology review
Muscular dystrophies and mitochondrial myopathies: Pathology review
Miscellaneous genetic disorders: Pathology review

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


0 / 8 complete


1 / 1 complete
High Yield Notes
5 pages

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

8 flashcards

USMLE® Step 1 style questions USMLE

1 questions

A 15-month-old boy comes to the office because of developmental delay. His parents state that he is still unable to walk or say more than one word at a time. The patient had an upper respiratory infection four weeks ago and another one three months ago. Physical examination shows coarse facial features, corneal clouding, rhinorrhea, and hepatosplenomegaly. Metabolic analysis shows elevated urinary glycosaminoglycans (GAGs). Which of the following enzyme deficiencies is the most likely cause of the patient's symptoms?

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.