Structural Biochemistry/Hurler Syndrome

Introduction to Hurler Syndrome

Hurler syndrome has an autosomal recessive pattern of inheritance.

Hurler syndrome, also known as mucopolysaccharidosis type I (MPS I) is a genetic disorder, inherited in an autosomal recessive manner, that results in the buildup of glycosaminoglycans (formerly called mucopolysaccharides). It is associated with storage and urinary excretion of the mucopolysaccharides dermatan sulfate and heparan sulfate.

Persons with Hurler syndrome do not make a substance called lysosomal alpha-L-iduronidase, an enzyme responsible for the degradation of mucopolysaccharides in lysosomes. This enzyme helps break down long chains of sugar molecules called glycosaminoglycans. These molecules are found throughout the body, often in mucus and in fluid around the joints. Without this enzyme, a buildup of heparan sulfate and dermatan sulfate occurs in the body.

Symptoms

Symptoms of Hurler syndrome most often appear between ages 3 and 8. Infants with severe Hurler syndrome appear normal at birth. Facial symptoms may become more noticeable during the first 2 years of life.

Symptoms include:

1. Abnormal bones in the spine
2. Claw hand
3. Cloudy corneas
4. Deafness
5. Halted growth
6. Heart value problems
7. Joint disease, including stiffness
8. Mental retardation that gets worse over time
9. Thick, coarse facial features with low nasal bridge

Signs and tests

1. Genetic testing for the alpha-L-iduronidase (IDUA) gene
2. Urine tests for extra mucopolysaccharides
3. X-ray of the spinal cord

Treatment

Enzyme replacement therapy adds a working form of the missing enzyme to the body. Bone marrow transplant has been used in several patients with this condition. The treatment has had mixed results. Other treatments depend on the organs that are affected.

Classification

MPS I is divided into three subtypes based on the severity of symptoms. All of the MPS types are due to the lack of the enzyme α-L-iduronidase. MPS I H or Hurler syndrome is the most severe of the three. The other two types are Scheie syndrome and Hurler-Scheie syndrome. Hurler syndrome is often classified as a lysosomal storage disease, and is clinically related to Hunter Syndrome. Hunter is X-linked while Hurler is autosomal recessive.

References

1. eMedicine Specialties > Mucopolysaccharidosis Type I Author: Maryam Banikazemi. Updated: Apr 14, 2009
2. Wraith JE. Mucopolysaccharidoses and oligosaccharidoses. In: Fernandes J, Saudubray J-m, van den Berghe G, Walter JH, eds. Inborn Metabolic Diseases: Diagnosis and Treatment. 4th ed. New York, NY: Springer;2006:chap 39.
3. Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, California 90095-1737, USA. neufeld@mednet.ucla.edu