Hurler Syndrome

Hurler Syndrome

Overview

Hurler syndrome is the most severe form of mucopolysaccharidosis type 1 (MPS 1). It’s an autosomal recessive condition.

MPS 1 is a condition where your body doesn't have enough enzymes to break down sugar molecules (glycosaminoglycans, formerly called mucopolysaccharides). The condition causes skeletal/joint abnormalities, distinct facial characteristics, issues with cognitive development, heart and lung (respiratory) problems and an enlarged liver and spleen.

Hurler syndrome is a lysosomal storage condition. When your body is unable to break down molecules normally, they accumulate in lysosomes. Lysosomes are the parts of your cell that control molecular waste management (the storage, recycling and digestion of molecules). When there’s too much toxic molecular buildup in your cells, the cells quickly die or don’t function properly, which causes symptoms of the condition.

Life expectancy for children diagnosed with Hurler syndrome is short due to life-threatening symptoms.

What are other types of mucopolysaccharidosis type I?

There are three types of Mucopolysaccharidosis type I (MPS I), including:

Hurler syndrome.

Hurler-Scheie syndrome.

Scheie syndrome.

These types fall on a spectrum based on severity. On one side of the spectrum is Hurler syndrome, which is the most common, most severe and has life-threatening complications. On the other side of the spectrum are Hurler-Scheie syndrome (intermediate form) and Scheie syndrome (mild form). Your child's healthcare provider will most likely call the less severe forms of MPS I “attenuated MPS I.”

Hurler-Scheie and Scheie syndromes have symptoms that match Hurler syndrome, but the progression of the condition is slower. You might see symptoms when your child turns six or seven years old with attenuated MPS I, as opposed to seeing symptoms shortly after birth with Hurler syndrome.

When symptoms of attenuated MPS 1 show up, how they impact the person diagnosed with the condition varies greatly. People with attenuated MPS I can have a normal lifespan and children with Hurler syndrome have a short lifespan.

The main difference between the three types of MPS I is that Hurler syndrome causes major developmental delays during early childhood and affects a child’s intelligence significantly. Hurler syndrome also causes your child’s cognitive abilities to decline over time. Attenuated MPS I can affect a child’s intelligence but not at the same rate as Hurler syndrome.

Symptoms

Symptoms of Hurler syndrome range in severity and are unique to each person diagnosed with the condition. Symptoms begin in early childhood and continue through adolescence.

A symptom of Hurler syndrome that sets it apart from other levels of mucopolysaccharidosis type I (MPS 1) is early childhood developmental delays and a progressive decline in how your child can learn and retain information. Mild cases of MPS 1 don’t affect a child’s intelligence.

Symptoms of Hurler syndrome could include:

Heart valve problems (cardiomyopathy).

Hearing loss.

Buildup of cerebrospinal fluid around your child's brain (hydrocephalus).

Enlarged organs like connective tissues, tonsils, muscles, heart, liver and spleen.

Vision problems (glaucoma).

Joint problems (tight muscles, carpal tunnel and joint disease).

Respiratory infections, sleep apnea and difficulty breathing.

Hernias.

Physical characteristics

During a child’s first year, physical symptoms of Hurler syndrome will appear. These characteristics include:

Short stature.

Bones forming incorrectly (dysostosis).

Rounding curve of your child's upper back (thoracic-lumbar kyphosis).

Excessive hair growth.

Causes

A mutation of the IDUA gene causes Hurler syndrome. The IDUA gene is responsible for creating lysosomal enzymes, which break down waste in cells. When the IDUA gene doesn't create enough enzymes, toxic waste collects in cells, causing them to die or not function properly. When your cells can’t get rid of waste, symptoms of Hurler syndrome occur.

How is Hurler syndrome inherited?

Hurler syndrome is hereditary, which means you can get the condition from your parents. Hereditary conditions aren't the result of something your parent did while pregnant.

Cells form in your parent’s reproductive organs via one fertilized cell from the sperm and one from the egg. The cells divide and copy themselves with half the amount of DNA as the original cell. During this process of cell division, genetic mutations can occur randomly as cells re-type the instruction manual word for word. Any time there's a typo (genetic mutation), the genetic code for part of your DNA is incomplete. As a result, your cells don’t have the instructions they need to form and function properly.

Diagnosis and Tests

How is Hurler syndrome diagnosed?

Prenatal screening tests, like amniocentesis or chorionic villus sampling, can diagnose your child with Hurler syndrome while you’re pregnant. Both tests examine whether or not there are any genetic abnormalities within your baby’s DNA.

After your baby is born, their healthcare provider will diagnose Hurler syndrome with a physical examination to look for symptoms of the condition and enzyme activity assays to confirm the diagnosis. They'll also ask if you know of any family members who have mucopolysaccharidosis conditions, since it’s hereditary.

Additional tests, like an X-ray of your child's bones, echocardiogram of their heart, and blood and urine tests might be necessary to confirm the diagnosis.

Management and Treatment

How is Hurler syndrome treated?

Treatment for Hurler syndrome focuses on preventing and managing symptoms of the condition:

Enzyme replacement therapy (ERT): Replacing damaged enzymes can prevent symptoms from getting worse and has the potential to reverse complications. Your child's healthcare provider will schedule regular shots of alpha L-iduronidase (aldurazyme) early after a diagnosis. The frequency of the shots depend on the severity of your child's diagnosis and is a lifelong treatment option.

Hematopoietic stem cell transplant (HSCT): For children under two years old (and some over two years old, by the supervision of their provider) diagnosed with Hurler’s syndrome, HSCT can prolong life expectancy in severe cases, prevent disease progression, preserve cognitive function and reduce symptoms that affect their body (somatic). Stem cells from donors with functioning enzymes that are found in bone marrow (hematopoietic cells) replace damaged cells in a child via chemotherapy.

Other types of treatment options for Hurler syndrome include:

Surgery to alleviate symptoms, like repairing or replacing heart valves, cornea replacement, repairing bone growth abnormalities or repairing hernias.

Physical, occupational and/or speech therapy.

Receiving supplemental oxygen using a CPAP machine.

Using hearing aids.

Taking medicine to reduce pain associated with symptoms.

Are there complications from the treatment?

In some cases, people with Hurler syndrome may have complications related to the anesthetic given during surgical procedures. This happens because your child might have symptoms that cause breathing difficulties and their provider could have trouble securing an IV if they have tight muscles, joints or tissues (contractures).

The timing of treatment is important for it to be effective, especially for hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT). If symptoms relating to cognitive development are present, it might be too late for the treatment to work at its full potential.

Before your child begins treatment, talk with their healthcare provider about possible side effects or complications that could arise.

Type of Doctor Department :  A medical geneticist