MUCOPOLYSACCHARIDOSIS I (MPS I)

Mucopolysaccharidosis I, commonly known as MPS I, is a rare genetic disorder that affects the body’s ability to break down certain sugar molecules. This condition falls under the category of lysosomal storage disorders, where the body lacks specific enzymes needed to break down these molecules, leading to their accumulation within cells.

Mucopolysaccharidosis type I (MPS I) is a genetic disorder that manifests in childhood. It’s not contagious; instead, it results from inherited genes.

Individuals with MPS I lack a crucial enzyme called alpha-L-iduronidase, which is necessary for breaking down certain sugars. The absence of this enzyme leads to the accumulation of sugars in cells, causing widespread damage in the body.

Health Impact of Mucopolysaccharidosis I

MPS I can affect physical growth, bodily functions, and cognitive abilities. Individuals with this condition might also have distinct physical features.

Those with milder forms of MPS I often manage to attend school, work, and start families. For those with more severe forms, treatments are available to alleviate symptoms and slow disease progression.

Historically, MPS I was categorized into Hurler, Hurler-Scheie, and Scheie syndromes based on severity. Nowadays, doctors refer to it as a spectrum with two primary forms:

Severe
Attenuated (less severe)

Causes of Mucopolysaccharidosis I

MPS I is caused by a deficiency in the enzyme alpha-L-iduronidase, which is essential for breaking down certain complex sugar molecules called glycosaminoglycans (GAGs). Without this enzyme, GAGs accumulate in cells and tissues throughout the body, leading to the characteristic symptoms of the disorder. MPS I is an inherited condition, requiring both parents to pass down a defective gene. If an individual inherits one normal gene and one defective gene, they will not exhibit symptoms of MPS I but can pass the defective gene to their offspring.

Prevalence

MPS I is a rare disorder, with an estimated incidence of 1 in 100,000 live births worldwide. However, the prevalence may vary among different populations and geographic regions.

Symptoms of Mucopolysaccharidosis I

Early Signs and Diagnosis

Initially, many babies with MPS I may not exhibit noticeable symptoms. In cases of attenuated (less severe) MPS I, symptoms typically emerge later in childhood. Children with this form likely produce a small amount of the necessary protein, resulting in milder symptoms and a slower disease progression.

Severe MPS I Symptoms

Children with severe MPS I often begin showing symptoms in infancy. These children may be larger at birth and grow rapidly during their first year, but their growth slows significantly by age three, with many not exceeding four feet in height. They also tend to share distinct physical characteristics:

Short stature with a stocky build
Large head and prominent forehead
Thick lips, widely spaced teeth, and large tongue
Short, flat nose with wide nostrils
Thick, tough skin
Short, broad hands with curved fingers
Knock-knees and a tendency to walk on toes
Curved spine

Variety of Symptoms

MPS I can present with a wide range of symptoms, including:

Eye Problems: Cloudy corneas, difficulty seeing in bright light or at night
Dental Issues: Bad breath, dental problems
Weak Neck
Respiratory Issues: Breathing problems, frequent airway infections, runny nose, sinus infections, sleep apnea
Ear Issues: Frequent ear infections, hearing loss
Neurological Symptoms: Numbness and tingling in fingers or feet
Cardiovascular Problems: Heart disease
Musculoskeletal Issues: Stiff joints, difficulty moving
Hernias: Bulges around the belly button or groin
Gastrointestinal Issues: Diarrhea
Organ Enlargement: Enlarged liver or spleen

Children with milder forms of MPS I often have fewer physical problems, typically maintain normal intelligence, and can engage in many activities similar to their peers. Conversely, severe MPS I can lead to a greater number of these symptoms, potentially impacting cognitive abilities and learning. Some children with severe MPS I may also lose the ability to speak.

Risk Factors

The primary risk factor for MPS I is having a family history of the disorder. It is inherited in an autosomal recessive pattern, meaning that both parents must carry a copy of the defective gene for a child to be affected.

Diagnosis of Mucopolysaccharidosis I

Diagnosing MPS I can be challenging due to its rarity. Doctors often begin by ruling out more common conditions. Your doctor may ask the following questions to understand the symptoms better:

What symptoms have you noticed?
When did these symptoms first appear?
Are the symptoms consistent, or do they come and go?
Is there anything that improves or worsens the symptoms?
Has anyone in your family experienced similar symptoms?

Diagnostic Tests

If other conditions are ruled out and MPS I is suspected, the following tests can confirm the diagnosis:

Urine Test: Checking for elevated levels of specific sugars.
Blood or Skin Cell Test: Measuring the activity of the deficient enzyme, alpha-L-iduronidase.

Once MPS I is confirmed, informing extended family members about the genetic nature of the condition is advisable.

Prenatal Testing

If you are pregnant, a known carrier of the MPS I gene, and already have a child with MPS I, prenatal testing can determine if the unborn child is affected. Discuss testing options with your doctor for early intervention.

Treatments for Mucopolysaccharidosis I

While there is currently no cure for MPS I, various treatments are available to manage the symptoms and improve quality of life. These may include:

Enzyme Replacement Therapy (ERT)

Enzyme replacement therapy (ERT) involves the administration of laronidase (Aldurazyme), a synthetic version of the deficient enzyme. This treatment has significantly improved the outlook for many children with MPS I, alleviating most symptoms and slowing disease progression. However, ERT does not address neurological symptoms such as cognitive or learning difficulties.

Hematopoietic Stem Cell Transplant (HSCT)

Another potential treatment is a hematopoietic stem cell transplant (HSCT), where new cells are introduced into the child’s body to produce the missing enzyme. These cells are usually sourced from bone marrow or umbilical cord blood. If performed before the age of two, HSCT can enhance cognitive development. However, it does not resolve bone or eye issues.

Specialist Care

It is crucial to work with a doctor specializing in lysosomal storage diseases (LSDs). Depending on the symptoms, other specialists may be needed, including cardiologists for heart-related issues and ophthalmologists for eye care.

Home Care Tips

For individuals with MPS I, home care may involve:

Regular monitoring of symptoms and complications
Following a healthy diet and exercise regimen
Making modifications to the home environment to accommodate mobility and accessibility needs
Seeking emotional and social support from family, friends, and support groups

Prevention

Since Mucopolysaccharidosis I is a genetic disorder, it cannot be prevented. However, genetic counseling and testing can help identify carriers of the defective gene and inform family planning decisions.

When to See a Doctor

If you or your child experiences any of these concerning symptoms, it’s crucial to see a doctor promptly for a proper evaluation and potential MPS I testing:

Developmental Delays: Milestones like walking, talking, and learning new skills may be delayed in children with MPS I.
Unusual Facial Features: A coarse facial appearance, thickened features, and a distinctive broad nose can be signs of MPS I.
Frequent Infections: Frequent ear infections, respiratory problems, and other infections can occur in individuals with MPS I due to a weakened immune system.

Supporting Your Child

Encouraging independence and social interactions is vital for children with MPS I, who often enjoy and benefit from spending time with others. Here are some ways to support your child:

Encouragement and Positivity: Foster independence and social engagement. Children with MPS I often thrive in social settings.
Communication: Educate others about your child’s condition to ease social interactions. Share details about what your child can do, their interests, and personality.
Education: Collaborate with school staff to develop an individualized education program (IEP). Your child may need personalized attention, special desks, or other accommodations in the classroom.
Safety: Avoid high-risk activities such as contact sports, gymnastics, and trampolines to protect your child’s neck.
Home Adaptations: Modify your home to enhance mobility and independence for your child.
Self-Care for Caregivers: Take breaks to rest and recharge, and allow others to help with caregiving duties when needed.

What to Expect

Although MPS I has no cure, early and ongoing treatments can greatly improve the quality of life by slowing disease progression and preventing further damage.

Milder Forms: Children with less severe MPS I can attend school, go through puberty, and potentially have children of their own. Adults with MPS I are protected by the Americans with Disabilities Act (ADA), allowing them to work and live independently.
Severe Forms: The severe form progresses rapidly, often leading to significant deterioration. Children with the most severe form may not live into their teenage years. In these cases, care focuses on pain relief and support to ensure the best possible quality of life.

Finding Support

For more information and support regarding MPS I, visit the National MPS Society website. This resource offers connections with others living with the disease and additional valuable information.

Outlook/Prognosis

The outlook for individuals with MPS I varies depending on the severity of the condition and the effectiveness of treatment. With early diagnosis and appropriate management, many individuals can lead fulfilling lives despite the challenges posed by the disorder. However, severe forms of MPS I can significantly impact life expectancy and quality of life.

Sources

Photo Credit: Medline plus
National MPS Society.
National Organization for Rare Disorders (NORD).
U.S. National Library of Medicine. Genetics Home Reference.
Genetics Home Reference
Illinois Department of Public Health
MPSI Research Foundation

Mucopolysaccharidosis I