What is Hurler Syndrome?
Hurler syndrome, first talked about by German pediatrician Gertrud Hurler in 1919, is a rare disorder that fits into a category of 11 conditions known as mucopolysaccharidoses (MPS). To put it simply, it’s often called mucopolysaccharidosis type I or MPS I. People used to refer to it as gargoylism. In 1962, doctors identified a less severe version of this condition and named it Scheie syndrome.
This condition is a result of a genetic issue that affects the body’s cells. Specifically, it is caused by the absence of an enzyme known as alpha-L-iduronidase. This enzyme’s job is to break down certain complex sugars in the body (Glycosaminoglycans or GAG). Without this enzyme, these sugars build up in various tissues in the body, causing ongoing decline in health leading to a risk of death.
What Causes Hurler Syndrome?
Hurler syndrome is a disorder that someone inherits from their parents, which involves a faulty gene. This gene, normally responsible for producing an enzyme called alpha-L-iduronidase (IUDA), is located on the 4th chromosome. For people with Hurler syndrome, this enzyme doesn’t function as it should.
Risk Factors and Frequency for Hurler Syndrome
Hurler syndrome is a rare condition that affects about 1 in every 100,000 births. This syndrome does not discriminate — it affects boys and girls equally, and is a risk for all races and ethnicities.
Signs and Symptoms of Hurler Syndrome
Hurler syndrome is a condition that usually begins to show symptoms during a child’s first year of life. There are various signs that parents might notice as their child develops. Characteristic physical features include a large head with protruding eyes, a flat nose, enlarged lips, and a short, stiff neck. The child could face developmental delays and might lose skills they had previously learned. Common health issues can include frequent infections in the ears, sinuses, and lungs, as well as heart problems.
Other specific manifestations involve different body systems and can include:
- Neurological: Progressively worsening developmental delay and potential seizures due to an accumulation of substances known as GAGs in the brain and spinal cord.
- Respiratory: Frequent infections and sleeping problems due to changes and blockages in the nose, throat, and lungs.
- Cardiac: Heart diseases including cardiomyopathy, endocardial fibroelastosis, valvular regurgitation, and heart failure.
- Gastrointestinal: Swallowing difficulties, resulting in speech impairments and the appearance of hernias early in life.
- Musculoskeletal: Stunted growth by age 2, and skeletal abnormalities like a rapidly enlarging head size and joint stiffness.
- Ocular: Clouding of the cornea leading to blindness, retinal degeneration, and optic nerve compression.
- Hearing: Buildup of GAGs in the middle ear causing recurrent ear infections and hearing loss.
- Integumentary: Abnormalities in skin and hair, like coarse, abundant hair and bluish birthmarks known as Mongolian spots.
Without treatment, most children with severe Hurler syndrome unfortunately do not live past the age of 10. It is recommended for patients to undergo cardiac evaluations every 1 or 2 years after their initial diagnosis.
Testing for Hurler Syndrome
If your doctor believes you might have Hurler syndrome, they will conduct a comprehensive medical examination and then have you take a specific urine test. While this test is a useful starting point, it can accidentally report no presence of the disease even when it exists.
If you have a family history of Hurler syndrome, it usually increases the chances that you might have the disease.
There are also tests that measure the activity of specific enzymes in your body. These tests are the most reliable way to confirm if you have Hurler syndrome. They utilize samples from different parts of your body like skin cells, white blood cells, plasma, or serum.
Not only can these tests confirm Hurler syndrome, but they can sometimes also help differentiate it from other related conditions based on how severe your symptoms are and when they first began.
If you are expecting a baby, there are tests that can be done to find out if your unborn child has Hurler syndrome. These tests measure enzyme activity in samples taken from the placenta or from cells in the amniotic fluid surrounding your baby.
Finally, gene sequencing can identify if there are any genetic changes associated with Hurler syndrome within your family. This is mostly beneficial for those with a family history of the disease as it provides information needed for genetic counseling and carrier tests. These help families make informed decisions when planning for children.
Treatment Options for Hurler Syndrome
Hurler syndrome is a condition with available therapies mainly aimed at managing complications, rather than addressing the root cause itself. One of these treatments is enzyme replacement therapy, which uses a man-made version of a naturally occurring enzyme called alpha-L-iduronidase. This is delivered via intravenous (IV) injection weekly and achieves better results when administered before severe complications occur. This therapy primarily benefits patients with Hurler and Hurler-Scheie types of the syndrome (called MPS I), and those with moderate-to-severe symptoms associated with the Scheie form.
Another strategy is a hematopoietic stem cell transplant (HSCT), a process which gradually replaces enzyme-deficient blood cells with healthy ones from a donor. This is thought to be the best treatment for patients under 2 years old and also benefits some according to their specific conditions. The transplant can prolong survival, reduce symptoms like enlarged liver and spleen, improve heart function, joint mobility and hearing, primarily in younger patients. However, it’s worth noting that HSCT is more effective at stopping the disease from getting worse, rather than reversing the damage already done.
Additional supportive treatment for Hurler syndrome includes various surgeries, such as those for hernias and heart valves, physical, occupational, and speech therapies, and respiratory support like constant pressurized ventilation with added oxygen, often referred to as ‘CPAP’. Also, aids like hearing devices, medications for pain and gastrointestinal issues can be prescribed. In cases with vision issues, corneal transplants might be an option, but surgery on patients with Hurler syndrome can face complications from anesthesia.
New therapies are continually under investigation, especially in the field of gene therapy. Researchers are exploring ways of delivering the necessary enzyme’s gene using viral vectors for potential treatment in the future. Initial studies in animal models have shown promising results, including improvements in vital organs like the liver, spleen, and brain. Potentially, gene therapy could become an alternative treatment for MPS disorder, a group of conditions including Hurler syndrome.
What else can Hurler Syndrome be?
Hunter syndrome (also known as mucopolysaccharidosis type 2) and Sly syndrome (mucopolysaccharidosis type 6) are two medical conditions that show symptoms similar to Hurler syndrome. However, they have their unique characteristics:
- Hunter syndrome often emerges later and progresses more slowly than Hurler syndrome. An interesting point to note about Hunter syndrome is that it doesn’t involve any corneal (eye) manifestations unlike Hurler syndrome.
- Sly syndrome is a rare disorder that also mirrors Hurler syndrome. However, the mental retardation that can accompany Sly syndrome may be absent or just mild. The most common symptom of Sly syndrome is a condition called Hydrops fetalis, because of which patients often don’t survive long enough to be diagnosed.
What to expect with Hurler Syndrome
The average life span for individuals with MPS, a rare genetic disorder, is around 8.7 years. However, this can vary depending on whether or not the patient receives a bone marrow transplant. Patients who have a successful bone marrow transplant have a 68% chance of living for another 2 years and a 64% chance of living for another 10 years.
On the other hand, those who do not receive the transplants have a significantly shorter average life expectancy, around 6.8 years.
