Morquio Syndrome: Symptoms, Causes, Treatment

What are the symptoms of Morquio syndrome?

Mucopolysaccharidosis type I, also known as Morquio syndrome, is a rare genetic disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. The symptoms of Morquio syndrome can vary in severity and may include:

Short stature: Patients with Morquio syndrome typically have short stature due to growth plate abnormalities.
Intellectual disability: Many individuals with Morquio syndrome have intellectual disability, ranging from mild to severe.
Dysostosis multiplex: Morquio syndrome is characterized by dysostosis multiplex, a condition that affects the growth plates of the bones, leading to skeletal deformities.
Corneal clouding: Clouding of the corneas (corneal clouding) can occur due to the accumulation of glycosaminoglycans in the corneal tissue.
Hepatosplenomegaly: Enlargement of the liver and spleen (hepatosplenomegaly) due to the accumulation of stored materials in these organs.
Joint stiffness and limited mobility: Patients with Morquio syndrome often experience joint stiffness and limited mobility due to the accumulation of glycosaminoglycans in the joints.
Respiratory problems: Respiratory problems, such as bronchitis and pneumonia, can occur due to the accumulation of mucopolysaccharides in the lungs.
Cardiac problems: Some individuals with Morquio syndrome may experience cardiac problems, such as hypertrophic cardiomyopathy or valve disease.
Eye problems: Eye problems, such as cataracts, glaucoma, and retinal detachment, can occur due to the accumulation of glycosaminoglycans in the eye tissue.
Skeletal deformities: Patients with Morquio syndrome may develop skeletal deformities, such as kyphosis, scoliosis, and claw hand.
Dental problems: Dental problems, such as tooth decay and gum disease, can occur due to the accumulation of glycosaminoglycans in the mouth.

It’s essential to note that the symptoms of Morquio syndrome can vary in severity and progression, and some individuals may have a milder form of the disorder while others may have a more severe form.

What are the causes of Morquio syndrome?

Morquio syndrome, also known as Mucopolysaccharidosis type I, is a rare genetic disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. This enzyme is responsible for breaking down glycosaminoglycans, which are complex carbohydrates found in the body.

The causes of Morquio syndrome can be attributed to mutations in the IDS gene, which codes for the iduronate-2-sulfatase enzyme. These mutations can result in a deficiency or complete absence of the enzyme, leading to the accumulation of glycosaminoglycans in the body.

The mutations that cause Morquio syndrome can be:

Point mutations: Single-point mutations that alter the DNA sequence of the IDS gene.
Deletions: Deletions of one or more nucleotides in the IDS gene.
Insertions: Insertions of one or more nucleotides in the IDS gene.
Frameshift mutations: Mutations that alter the reading frame of the IDS gene, leading to a premature stop codon.
Splice site mutations: Mutations that affect the splicing of the IDS gene, leading to an abnormal protein product.

These genetic mutations can be inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop Morquio syndrome. If a person inherits only one copy of the mutated gene, they may be a carrier of the condition but will not develop symptoms themselves.

In some cases, Morquio syndrome can also occur due to a lack of functional enzyme activity, even if there is no detectable mutation in the IDS gene. This can occur due to various factors such as:

Enzyme substrate specificity: The iduronate-2-sulfatase enzyme may have altered substrate specificity, making it unable to effectively break down glycosaminoglycans.
Protein folding defects: The iduronate-2-sulfatase protein may have an altered structure or folding pattern, rendering it inactive or unstable.
Post-translational modifications: Post-translational modifications, such as phosphorylation or ubiquitination, may affect the activity or stability of the iduronate-2-sulfatase enzyme.

Overall, the causes of Morquio syndrome are complex and multifactorial, and further research is needed to fully understand the underlying mechanisms of this disorder.

How is the diagnosis of Morquio syndrome made?

The diagnosis of Morquio syndrome, also known as Mucopolysaccharidosis type I, is typically made through a combination of clinical evaluation, laboratory tests, and genetic analysis. The following steps are often involved in the diagnostic process:

Clinical evaluation: A thorough physical examination is performed to assess the patient’s overall health, growth, and development. The doctor may also review the patient’s medical history and family history.
Laboratory tests: Several laboratory tests are used to help confirm the diagnosis:
- Enzyme assay: A blood test is performed to measure the activity of the iduronate-2-sulfatase enzyme. A low or absent enzyme activity level can indicate Morquio syndrome.
- Glycosaminoglycan analysis: A urine or blood test is performed to measure the levels of glycosaminoglycans in the body. Elevated levels of glycosaminoglycans can indicate Morquio syndrome.
- X-ray and imaging studies: Imaging studies such as X-rays, CT scans, or MRI scans may be performed to evaluate the patient’s skeletal system and identify any characteristic features of Morquio syndrome, such as joint stiffness or skeletal deformities.
Genetic testing: Genetic testing is used to identify the specific genetic mutation that causes Morquio syndrome. This can be done through:
- Direct DNA sequencing: The IDS gene is sequenced to identify specific mutations.
- Genetic linkage analysis: A family history is taken, and genetic linkage analysis is performed to identify the chromosomal region associated with Morquio syndrome.
Confirmatory testing: If the initial tests are suggestive of Morquio syndrome, confirmatory testing may be performed to rule out other conditions with similar symptoms.

The diagnosis of Morquio syndrome is often made by a team of healthcare professionals, including pediatricians, geneticists, and specialists in orthopedics, ophthalmology, and cardiology. A comprehensive diagnostic evaluation is essential to ensure accurate diagnosis and appropriate treatment for the patient.

What is the treatment for Morquio syndrome?

The treatment for Morquio syndrome, also known as Mucopolysaccharidosis type I, is aimed at managing the symptoms and slowing down the progression of the disease. There is no cure for Morquio syndrome, but various treatments can help alleviate symptoms and improve the quality of life for affected individuals.

Enzyme replacement therapy (ERT): This is the primary treatment for Morquio syndrome. ERT involves injecting a recombinant iduronate-2-sulfatase enzyme into the bloodstream to replace the missing or defective enzyme. This helps to break down glycosaminoglycans and reduce their accumulation in the body.

Elaprase: Elaprase (idursinafon) is a recombinant iduronate-2-sulfatase enzyme that is approved by the FDA for the treatment of Morquio syndrome. It is administered every two weeks through an intravenous infusion.

Other treatments: In addition to ERT, other treatments may be used to manage specific symptoms and complications:

Physical therapy: To improve joint mobility and reduce stiffness.
Occupational therapy: To improve daily functioning and independence.
Speech therapy: To address speech and language difficulties.
Orthotics and assistive devices: To help with mobility and balance.
Surgical interventions: To correct skeletal deformities, such as joint contractures or spinal curvature.
Medications: To manage symptoms such as pain, respiratory infections, or sleep disorders.
Nutritional support: To ensure adequate nutrition and prevent malnutrition.

Lifestyle modifications: Patients with Morquio syndrome should also make lifestyle modifications to help manage their condition:

Exercise regularly: Gentle exercises can help maintain joint mobility and reduce stiffness.
Maintain a healthy weight: A healthy weight can reduce pressure on joints and bones.
Avoid excessive physical activity: Avoid activities that may exacerbate joint pain or stiffness.
Stay hydrated: Drink plenty of fluids to help flush out excess glycosaminoglycans from the body.
Get regular check-ups: Regular follow-up appointments with healthcare providers are essential to monitor disease progression and adjust treatment as needed.

It’s essential for individuals with Morquio syndrome to work closely with their healthcare providers to develop a personalized treatment plan that addresses their specific needs and symptoms.

What is the life expectancy with Morquio syndrome?

The life expectancy for individuals with Morquio syndrome, also known as Mucopolysaccharidosis type I, is typically shorter than average. The prognosis varies depending on the severity of the disease and the effectiveness of treatment.

Without treatment: In the absence of enzyme replacement therapy (ERT), Morquio syndrome is often fatal in childhood or early adulthood due to respiratory complications, such as respiratory failure or pneumonia.

With treatment: With ERT, the life expectancy for individuals with Morquio syndrome has improved significantly. According to a study published in the Journal of Inherited Metabolic Disease, the median survival age for individuals with Morquio syndrome treated with ERT is approximately 45-50 years.

Factors influencing life expectancy: Several factors can influence the life expectancy of individuals with Morquio syndrome:

Severity of symptoms: Individuals with more severe symptoms, such as severe joint stiffness or skeletal deformities, may have a shorter life expectancy.
Age of onset: Children who develop Morquio syndrome at a younger age tend to have a poorer prognosis than those who develop it later in life.
Response to treatment: Individuals who respond well to ERT and other treatments tend to have a better prognosis than those who do not respond as well.
Complications: Presence of complications, such as respiratory or cardiac problems, can significantly impact life expectancy.
Genetic factors: The specific genetic mutation causing Morquio syndrome can also influence the prognosis.

It’s essential for individuals with Morquio syndrome to work closely with their healthcare providers to develop a comprehensive treatment plan that addresses their specific needs and helps manage their symptoms.