Summary about Disease
N-acetylgalactosamine-6-sulfate sulfatase deficiency (GALNS deficiency), also known as Morquio A syndrome (Mucopolysaccharidosis IVA), is a rare inherited metabolic disorder. It belongs to a group of diseases called mucopolysaccharidoses (MPS), which are characterized by the body's inability to properly break down certain complex sugar molecules called glycosaminoglycans (GAGs), also known as mucopolysaccharides. In Morquio A syndrome, a deficiency of the enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS) leads to the accumulation of keratan sulfate (a type of GAG) within cells, tissues, and organs. This accumulation causes a wide range of skeletal abnormalities and other symptoms. The severity of Morquio A syndrome varies widely from mild to severe.
Symptoms
Symptoms of Morquio A syndrome can vary significantly in severity and presentation. Common symptoms include:
Skeletal abnormalities: These are the most prominent feature and can include:
Skeletal dysplasia (abnormal bone development)
Short stature/dwarfism
Scoliosis (curvature of the spine)
Kyphosis (hunchback)
Pectus carinatum (pigeon chest) or pectus excavatum (sunken chest)
Hip dysplasia
Genu valgum (knock-knees)
Loose joints
Cardiac problems:
Heart valve abnormalities
Cardiomyopathy (weakening of the heart muscle)
Respiratory problems:
Restricted lung capacity due to skeletal abnormalities
Tracheal and bronchial cartilage abnormalities
Increased susceptibility to respiratory infections
Hearing loss:
Corneal clouding:
Dental abnormalities:
Enamel hypoplasia (thin or deficient enamel)
Neurological complications:
Spinal cord compression (due to skeletal abnormalities) leading to:
Weakness
Paralysis
Pain
Normal intelligence: Cognitive abilities are typically not affected.
Causes
Morquio A syndrome is caused by mutations in the GALNS gene. This gene provides instructions for making the enzyme N-acetylgalactosamine-6-sulfate sulfatase. Mutations in the *GALNS* gene reduce or eliminate the activity of this enzyme. As a result, keratan sulfate (a type of GAG) accumulates within cells, tissues, and organs, leading to the symptoms of the disorder. The condition is inherited in an autosomal recessive pattern, meaning that both parents must carry a copy of the mutated gene for their child to be affected.
Medicine Used
Enzyme Replacement Therapy (ERT): Elosulfase alfa (Vimizim) is an enzyme replacement therapy that provides a functional version of the GALNS enzyme. It is administered intravenously and aims to reduce keratan sulfate accumulation. ERT is approved for Morquio A syndrome.
Hematopoietic Stem Cell Transplantation (HSCT): In some cases, HSCT may be considered, but it does not reverse skeletal changes.
Other medications and treatments: Treatment is often supportive and focuses on managing the symptoms of the condition. This may include:
Pain relievers
Respiratory support (e.g., oxygen therapy, assisted ventilation)
Orthopedic surgery to correct skeletal abnormalities
Hearing aids
Physical therapy
Occupational therapy
Is Communicable
No, Morquio A syndrome is not communicable. It is a genetic disorder caused by mutations in the GALNS gene and cannot be spread from person to person.
Precautions
Since Morquio A syndrome is a genetic disorder, there are no precautions to prevent it in an individual who has inherited the mutated genes. However, genetic counseling and testing can be helpful for families with a history of the condition who are planning to have children. Precautions focus on managing the symptoms and complications of the disease:
Regular monitoring: Regular check-ups with specialists (e.g., orthopedic surgeons, cardiologists, pulmonologists, audiologists) are essential to monitor disease progression and manage complications.
Vaccinations: Regular vaccinations are recommended to help prevent respiratory infections.
Avoidance of activities that could cause spinal cord injury: Due to the risk of spinal cord compression, activities that could potentially cause trauma to the spine should be avoided.
Early intervention: Early intervention with therapies such as physical and occupational therapy can help maximize mobility and independence.
How long does an outbreak last?
Morquio A syndrome is not an infectious disease that causes "outbreaks". It is a chronic, progressive genetic disorder that persists throughout the individual's life.
How is it diagnosed?
Diagnosis of Morquio A syndrome typically involves a combination of:
Clinical evaluation: Based on physical examination, assessment of symptoms, and family history.
Urine tests: Elevated levels of keratan sulfate in the urine can suggest Morquio A syndrome.
Enzyme assay: Measuring the activity of the GALNS enzyme in white blood cells or fibroblasts. A deficiency of the enzyme confirms the diagnosis.
Genetic testing: Sequencing the GALNS gene to identify mutations.
Radiographic studies: X-rays, MRI, and CT scans to assess skeletal abnormalities.
Echocardiogram: To evaluate heart valve function.
Pulmonary function tests: To assess lung function.
Audiometry: To assess hearing.
Timeline of Symptoms
The timeline of symptom onset and progression can vary significantly among individuals with Morquio A syndrome. Some individuals may have subtle symptoms in early childhood, while others may not be diagnosed until later in life. A general timeline:
Infancy/Early Childhood: Some skeletal abnormalities may be present at birth, but often become more apparent in early childhood (1-3 years). Growth may slow down.
Childhood: Skeletal abnormalities such as scoliosis, knock-knees, and short stature become more prominent. Respiratory problems may begin to develop. Cardiac issues may become apparent. Hearing loss may be detected.
Adolescence/Adulthood: Skeletal deformities may progress, leading to increased pain and disability. Respiratory and cardiac complications may worsen. Spinal cord compression can occur at any age.
Important Considerations
Variability: The severity of Morquio A syndrome varies widely. Some individuals may have a relatively mild course, while others may experience significant disability and life-threatening complications.
Multidisciplinary care: Management of Morquio A syndrome requires a multidisciplinary team of specialists, including orthopedic surgeons, cardiologists, pulmonologists, neurologists, geneticists, physical therapists, and occupational therapists.
Spinal cord compression: Spinal cord compression is a serious complication that can lead to paralysis and other neurological problems. Early detection and treatment are crucial.
Anesthesia risks: Individuals with Morquio A syndrome are at increased risk of complications during anesthesia due to airway abnormalities and potential for spinal cord compression. Careful pre-operative evaluation and planning are essential.
Quality of life: While Morquio A syndrome can significantly impact quality of life, with appropriate medical care, supportive therapies, and a strong support system, individuals can live fulfilling lives.
Genetic Counseling: Genetic counseling is important for families affected by Morquio A syndrome to understand the inheritance pattern, recurrence risk, and options for prenatal testing.
Research: Ongoing research is focused on developing new treatments and improving the management of Morquio A syndrome.