What are the other Names for this Condition? (Also known as/Synonyms)

• Hurler Syndrome
• MPS1
• Mucopolysaccharide Storage Disease Type I

What is Mucopolysaccharidosis Type I? (Definition/Background Information)

• Mucopolysaccharidosis Type I (MPS I or Hurler Syndrome) is a rare, genetic metabolic condition that involves an inability of the body to breakdown glycosaminoglycans, which are long chains of sugar molecules. The condition is inherited in an autosomal recessive manner, meaning two copies (one from each parent) of the faulty gene are needed to cause signs and symptoms of the disorder
• The inheritance of the faulty genes prevents the body from producing an enzyme (known as the alpha-L iduronidase enzyme) that is responsible for breaking down the sugar molecules. This inability to breakdown these sugars, causes it to buildup leading to many defects
• Since Mucopolysaccharidosis Type I is genetic, it is present at birth. Significant signs and symptoms are seen between ages 3 to 8 years in children, which include abnormal facial features, cloudy corneas, abnormal development of spine, heart valve defects, and short stature in children
• A healthcare professional can use various diagnostic tools, such as a physical exam, electrocardiogram, urinalysis (analysis of urine), and X-rays of the affected regions, to help diagnose Mucopolysaccharidosis Type I
• There is no cure for Mucopolysaccharidosis Type I; however, the treatment provided is symptomatic. These can include enzyme replacement, bone marrow transplant, and other organ specific treatments
• Prognosis for children with Mucopolysaccharidosis Type I is poor; it often involves death at a young age. Complications, such as nervous system and heart defects, are generally life-threatening that can lead to fatalities

Based on the severity of signs and symptoms, Mucopolysaccharidosis Type I is subdivided into 2 categories:

• Severe type of MPS Type I; when individuals have severe signs and symptoms. The severe type is 5-times more common than the attenuated type
• Attenuated type of MPS Type I; when individuals have less severe or milder signs and symptoms

Who gets Mucopolysaccharidosis Type I? (Age and Sex Distribution)

• Mucopolysaccharidosis Type I is a rare congenital disorder, meaning that it is present at birth. The incidence of the condition is:
  • 1 in 100,000 live births for severe type of MPS Type I
  • 1 in 500,000 live births for attenuated type of MPS Type I
• The signs and symptoms are usually observed at 6 months. Although, significant features of the disorder often develop between the ages 3 to 8 years
• This inherited genetic disorder can affect males and females of different races and ethnic backgrounds

What are the Risk Factors for Mucopolysaccharidosis Type I? (Predisposing Factors)

• A genetic predisposition due to family history increases the risk for Mucopolysaccharidosis Type I

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Mucopolysaccharidosis Type I? (Etiology)

• Mucopolysaccharidosis Type I is caused by inheriting faulty genes that prevents the body from producing a certain enzyme, known as the alpha-L iduronidase enzyme. The gene responsible for MPS Type I is the IDUA gene. The condition is inherited in an autosomal recessive manner
• The enzyme is responsible for breaking down long chains of sugars, called glycosaminoglycans (GAGs). Due to a lack of production of this enzyme, GAG sugar molecules get abnormally accumulated in a structure called lysosome within the cells. The disorder is a kind of “lysosomal storage disease”, because the accumulation within special compartments of the cells, called lysosomes
• Lysosomes are a kind of recycling plant within the cells - they breakdown larger, more complex organic molecules into smaller molecules, which the cells can then reuse. When important enzymes are not functioning efficiently, the lysosomes become bloated and eventually, the cell gets ‘filled-up’ being unable to function anymore, leading to a disease state
• Mucopolysaccharidosis Type 1 is also known as Hurler Syndrome. The complex molecules glycosaminoglycans used to be called “mucopolysaccharides”; the term “mucopolysaccharidosis” literally means an overabundance of mucopolysaccharides

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected). 

What are the Signs and Symptoms of Mucopolysaccharidosis Type I?

Mucopolysaccharidosis Type I is a congenital disorder; noticeable features of the disorder are seen when the baby is around 6 months old. Facial symptoms may arise during the first 2 years of life. The onset of significant signs and symptoms occur when the child is between 3 to 8 years old. Children with severe type of MPS Type I have an earlier onset of signs and symptoms compared to those with the attenuated type.

The signs and symptoms of Mucopolysaccharidosis Type I may include:

• Thick, coarse facial features; enlarged skull
• Presence of large tongue (macroglossia)
• Abnormal development of vocal cords; individuals have deep, hoarse voice
• Abnormal bone growth in the spine, narrowing of the spine
• Cloudy cornea
• Frequent ear infection, hearing difficulties
• Stunted growth
• Degenerative joints causing joint stiffness
• Sleep disorder such as sleep apnea
• Decrease in mental cognition
• Enlarged liver (hepatomegaly) and enlarged spleen (splenomegaly)

How is Mucopolysaccharidosis Type I Diagnosed?

Diagnostic tools used by a healthcare provider in the diagnosis of Mucopolysaccharidosis Type I can include:

• Physical examination and analysis of previous medical history
• Peripheral smear exam may reveal abnormal lymphocytes containing cytoplasmic inclusions
• Urine tests: Increased levels of dermatan sulfate and heparin sulfate may be seen
• Hearing tests
• Sleep studies may be performed
• X-ray of different parts of the body may reveal bony abnormalities
• Electrocardiogram (EKG) to test the heart function
• Echocardiogram to determine heart defects
• MRI scan of brain to determine brain defects
• Genetic testing for changes in specific genes
• In many cases, the diagnosis is confirmed in the lab by a test called alpha-L-iduronidase enzyme assay, performed on fibroblast cells or leukocytes

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Mucopolysaccharidosis Type I?

Complications of Mucopolysaccharidosis Type I may include:

• Inguinal hernia causing a bulge on the side of the pubic bone, abdominal weakness, numbness in the groin, groin pain especially while coughing or lifting heavy objects
• Umbilical hernia causing an usually painless, soft bulge at the navel; the bulge is more visible when the baby cries or coughs
• Deafness
• Short stature
• Frequent incidence of pneumonia
• Heart valve defects; congestive heart failure
• Nervous system defects including fluid buildup in the brain (hydrocephalus)
• Decrease in mobility due to bone and joint defects
• Carpal tunnel syndrome causing hand signs and symptoms such as radiating pain within the hand, tingling sensation and numbness, weakness in strength of hand muscles, etc.
• Decreased life span

How is Mucopolysaccharidosis Type I Treated?

There is no cure for Mucopolysaccharidosis Type I, since it is a genetic condition. Treatment for MPS Type I is dependent on individual signs and symptoms and based on the organs that are affected. Since, this congenital condition involves various parts of the body and body systems, a team of healthcare professionals of diverse specialties are needed to manage MPS I. An individualized treatment (case-by-case approach) is provided to improve the quality of life. This is also based on the specific set of signs and symptoms and complications that develop in each child/individual.

The treatment measures may include:

• Enzyme replacement therapy: Replacement of the missing enzyme to help in the breakdown of glycosoaminoglycans
• Bone marrow transplant
• Other organ specific treatments as specified by the healthcare provider including:
  • Orthopedic surgery for correcting bone and joint abnormalities
  • Hernia repair for inguinal and umbilical hernia
  • Corneal transplant for vision abnormalities
  • Tonsillectomy for frequent ear and throat infections
  • Correction of hearing defects
  • Surgical treatment for carpal tunnel syndrome
• For improving motor skills and mental disabilities, special therapeutic treatment (by physical and occupational therapists) and supportive care is required
• Research is being currently undertaken to treat Mucopolysaccharidosis Type I using gene therapy

How can Mucopolysaccharidosis Type I be Prevented?

• Currently, there are no specific methods or guidelines to prevent Mucopolysaccharidosis Type I, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Mucopolysaccharidosis Type I
• Regular medical screening at periodic intervals with tests, scans and physical examinations are mandatory

What is the Prognosis of Mucopolysaccharidosis Type I? (Outcomes/Resolutions)

• Mucopolysaccharidosis Type I (Hurler Syndrome) is a progressive disorder that has a poor prognosis due to children developing nervous system and heart valve defects, which are often fatal
• The median survival rate is 11.5 years; many children die within the first 12 months
• The severe type has worse prognosis than the attenuated type of MPS Type I

Additional and Relevant Useful Information for Mucopolysaccharidosis Type I:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/congenital-genetic-disorders/