Hurler Syndrome

This page provides information about Hurler syndrome, its symptoms, causes and what treatment options are available.

Hurler syndrome is the most severe form of mucopolysaccharidosis type I (MPS I), a rare inherited lysosomal storage disease. In some countries, newborns are routinely screened for Hurler syndrome. If Hurler syndrome is suspected, the diagnosis is confirmed using enzyme activity testing and genetic testing. Hurler syndrome is also sometimes diagnosed prior to birth through prenatal genetic testing in families known to be at risk. 

Symptoms vary from child to child, usually starting in early childhood and sometimes becoming more severe over time. Many children experience developmental delays and a decline in learning ability. Quality of life and life expectancy are both impacted. 

The condition can affect many parts of the body, with symptoms potentially including:

• Heart - valve problems and cardiomyopathy 
• Brain and nervous system - hydrocephalus (fluid buildup around the brain) and hearing loss 
• Organs - enlargement of the liver and spleen and swelling of the tonsils and connective tissues 
• Eyes - vision problems such as corneal clouding and glaucoma 
• Joints and muscles - stiffness and joint disease 
• Breathing - respiratory infections, sleep apnea and difficulty breathing 
• Abdomen - hernias 

Hurler syndrome is caused by a change (or mutation) in a gene called IDUA. Normally, this gene tells the body how to make an enzyme that breaks down certain complex sugar molecules called glycosaminoglycans (GAGs), that occur naturally in our cells. Without this enzyme, GAGs build up inside cells and gradually damage tissues and organs throughout the body.  

Hurler syndrome is hereditary. A child will only develop the condition if they inherit a faulty copy of the IDUA gene from both parents. Parents who carry just one faulty copy don't show any symptoms themselves, but they can still pass this copy on to their children. 

Early diagnosis and treatment are important, as the disease can progress quickly. 

The standard of care for Hurler syndrome is a hematopoietic stem cell transplant (HSCT), also called a bone marrow transplant. This treatment replaces a child's cells with healthy donor cells that are able to produce the missing enzyme. It can help slow down some symptoms, especially those affecting the brain and nervous system, however it can't undo damage that has already happened, and the transplantation does carry significant risks. 

Another option is enzyme replacement therapy (ERT). This involves weekly infusions of a manufactured version of the missing enzyme, which can help reduce the buildup of GAGs and ease some physical symptoms. However, because the enzyme does not cross the blood-brain barrier, it does not have an impact on neurological symptoms. 

ERT is sometimes used before HSCT to improve the condition of patients prior to transplantation. In some cases, ERT is continued after transplantation as well.

Even with treatment, many children continue to experience symptoms over time. Ongoing care from a team of specialists is usually needed to help manage how the condition affects the heart, joints, eyes, and other parts of the body. 

Researchers are working to develop new therapies that may address both the systemic and neurological manifestations of Hurler syndrome, aiming to target the underlying cause of disease.  

ProQR is developing an investigational therapy called AX-0422 for the treatment of Hurler syndrome. Learn more about how AX-0422 works. 

Yes. Around the world, there are patient organisations that offer information, advocacy, and practical support to people living with Hurler syndrome and their families.  

The Hurldersyndrome.org webpage can help you find MPS societies and rare disease networks in your country or region. These organisations can connect you with resources, guidance, and communities of people who understand the challenges of living with Hurler syndrome.