Hurler Syndrome (MPS I Disease) Symptoms and Treatment

If you've learned that your child or a child of a loved one has Hurler syndrome, you're probably confused and frightened. What does this mean?

Definition

Hurler syndrome is a type of storage disease in the body caused by the lack of one enzyme. The abnormal enzyme, alpha -L-iduronidase (IDUA) is caused by a gene mutation in the IDUA gene, a gene located on chromosome 4. The condition varies in severity but is a progressive condition involving many bodily systems.

Understanding Mucopolysaccharidoses (MPS)

Mucopolysaccharidoses (MPS) are a group of genetic disorders in which critical body enzymes (chemicals) are missing or present in insufficient amounts. MPS I disease is caused by a deficiency in a particular enzyme called alpha-L-iduronidase (IUDA). 

The enzyme alpha-L-iduronidase breaks down long chains of sugar molecules so that the body can dispose of them. Without the enzyme, the big molecules of sugar build up and progressively damage parts of the body.

The build-up of molecules (glycosaminoglycans or GAGs) happens in the lysosomes (a special organelle in the cells that holds a variety of enzymes). The exact GAGs that build up in the lysosomes are different in each different type of MPS disease.

Hurler Syndrome or Hurler Disease is the historical term for the most severe version of MPS. Hurler was the last name of the doctor who first described the condition.

A baby will show few signs of the disorder at birth but within a few months (once molecules begin to build up in the cells) symptoms begin. Bone deformities may be detected. The heart and respiratory system are affected, as are other internal organs including the brain. The child grows but remains behind in both physical and mental development for his age.

The child may have trouble crawling and walking, and problems with his joints develop, causing parts of the body like his hands to be unable to straighten out. Children with Hurler syndrome usually succumb to problems such as heart failure or pneumonia.

Diagnosis

A diagnosis of Hurler syndrome is based on the child's physical symptoms. Generally, the symptoms of severe MPS I will be present during the first year of life, while the symptoms of attenuated MPS I appear in childhood. Testing may detect the decreased activity of the enzyme. It may also be possible to identify the disease in molecular genetic testing.

Testing

Prenatal testing for MPS I is part of the Recommended Uniform Screening Panel performed on newborns at 24 hours of age. Carrier testing for at-risk family members is present, but only if both IUDA gene variants have been identified in the family.

Many specialists are involved in the care of an individual with MPS I. A genetic counselor can talk with the family and relatives about the risks of passing on the syndrome.

Types

There are 7 sub-types of MPS disease and MPS I is the first subtype (the others are MPS II (Hunter syndrome), MPS III (Sanfilippo syndrome), MPS IV, MPS VI, MPS VII, and MPS IX).

Ranges

MPS I is considered to exist on a spectrum from mild (attenuated) to severe: There is a significant overlap between these and no significant biochemical differences have been identified between these.

• The mild, or attenuated form of MPS I is also known as Scheie syndrome or MPS I S: Children born with this form have normal intelligence and may live to adulthood.
• The severe form of MPS I is known as Hurler syndrome or MPS I H: Children affected with the severe form may have mental retardation, short stature, stiff joints, speech and hearing impairment, heart disease, and a shortened lifespan. These children often appear normal at birth with non-specific symptoms developing during the first year of life. For example, in the first year of life, they may have respiratory infections or an umbilical hernia, conditions found more often in children without the syndrome. Facial features become apparent during the first year, followed by widespread skeletal problems. By the age of three growth usually slows down significantly and intellectual and hearing problems become apparent.
• Some children may have normal intelligence and mild to severe physical symptoms; this condition may be called Hurler-Scheie syndrome or MPS I H-S.

These symptoms are very similar to those of MPS II (Hunter syndrome), but Hurler syndrome symptoms become worse much faster than Hunter syndrome type A.

Symptoms

Each of the MPS disorders can cause a variety of different symptoms, but many of the diseases share similar symptoms, such as:

• Corneal clouding (eye problems)
• Short stature (dwarfism or below typical height)
• Joint stiffness
• Speech and hearing problems
• Hernias
• Heart problems

Common symptoms specific to Hurler syndrome (and Scheie and Hurler-Scheie syndrome) include:

• Abnormal facial appearance (facial dysmorphism) described as "course" features
• Enlargement of the spleen and liver
• Upper airway obstruction
• Skeletal deformities
• Enlargement and stiffening of the heart muscle (cardiomyopathy)

Incidence

Globally, severe MPS I occurs in about 1 in every 100,000 births and is divided into three groups according to the type, severity, and the way the symptoms progress. Attenuated MPS I is less common, occurring in less than 1 in 500,000 births.

Inheritance

Hurler syndrome is inherited in an autosomal recessive pattern, meaning that a child must inherit two copies of the gene for MPS I, one from each parent, in order to develop the disease. 

Since the condition is hereditary, many parents who have a child with Hurler syndrome worry that other children could also be born with the missing enzyme. Since the condition is autosomal recessive, both parents are usually considered "carriers." This means that they have one copy of the gene which produces the enzyme normally, and one copy that does not. A child must inherit the defective genes from both parents.

The risk that two parents who are carriers will have a child with MPS I is 25 percent. There is also a 25 percent chance that a child will inherit normal copies of both genes. Half the time (50 percent) a child will inherit the defective gene from one parent and the normal gene from the other. These children will not have any symptoms but will be a carrier of the syndrome like his or her parents.

Treatment

There is as yet no cure for MPS I, so treatment has focused on relieving symptoms.

• Medication: Aldurazyme (laronidase) replaces the deficient enzyme in MPS I. Aldurazyme is given by intravenous infusion once per week for life to people with MPS I. Aldurazyme helps relieve symptoms but is not a cure.
• Stem Cell Transplant: Another treatment available for MPS I is a bone marrow transplant, which puts normal cells in the body that will manufacture the missing enzyme. However, many children with Hurler syndrome have heart disease and are not able to go through the chemotherapy required for the transplant. Stem cell transplant, when possible, may improve survival, intellectual decline, and cardiac and respiratory complications, but is much less effective in dealing with skeletal symptoms.