Overview

Morquio Syndrome, also known as Mucopolysaccharidosis Type IV (MPS IV), is a rare inherited metabolic disorder that affects the body's ability to break down certain complex carbohydrates known as glycosaminoglycans (GAGs). This leads to the buildup of GAGs in cells, particularly affecting bones, cartilage, and connective tissue. Morquio Syndrome results in skeletal abnormalities, short stature, joint problems, and various systemic complications. It is a progressive condition, meaning symptoms worsen over time, and it primarily manifests in early childhood.

Causes

Morquio Syndrome is caused by genetic mutations that lead to a deficiency of specific enzymes responsible for breaking down glycosaminoglycans:

• MPS IVA: Caused by mutations in the GALNS gene, leading to a deficiency of the enzyme N-acetylgalactosamine-6-sulfatase.
• MPS IVB: Caused by mutations in the GLB1 gene, leading to a deficiency of the enzyme beta-galactosidase.

Both types follow an autosomal recessive inheritance pattern, meaning a child must inherit two defective copies of the gene (one from each parent) to develop the condition.

Symptoms

Symptoms of Morquio Syndrome usually appear between the ages of 1 and 3 years and progressively worsen as the child grows. Common signs and symptoms include:

• Short stature: Growth slows after early childhood, leading to significantly shorter adult height.
• Skeletal abnormalities: Including a curved spine (kyphosis), chest protrusion, knock knees, and abnormal gait.
• Joint laxity: Hypermobile joints causing instability and difficulty walking.
• Facial features: Coarse facial features may develop, including a flat nasal bridge and enlarged head.
• Hearing loss: Progressive conductive or sensorineural hearing loss.
• Dental issues: Widely spaced teeth and enamel defects.
• Respiratory problems: Including obstructive sleep apnea, frequent lung infections, and breathing difficulties.
• Heart problems: Some individuals develop heart valve abnormalities.
• Normal intelligence: Cognitive development is typically unaffected, and most children have normal intellectual abilities.

Diagnosis

Diagnosis of Morquio Syndrome involves a combination of clinical evaluation, laboratory testing, and genetic analysis:

• Clinical examination: Identification of characteristic skeletal and physical features.
• Urine tests: Elevated levels of glycosaminoglycans (keratan sulfate) in urine can indicate MPS IV.
• Enzyme activity tests: Measurement of deficient enzyme activity in blood or skin fibroblasts confirms the diagnosis.
• Genetic testing: Identifies specific mutations in the GALNS or GLB1 genes.
• Imaging studies: X-rays, MRI, or CT scans are used to assess skeletal abnormalities and monitor disease progression.

Treatment

While there is no cure for Morquio Syndrome, treatment focuses on managing symptoms, improving quality of life, and slowing disease progression:

• Enzyme replacement therapy (ERT): Elosulfase alfa (for MPS IVA) can reduce GAG accumulation and improve endurance.
• Surgical interventions: Orthopedic surgeries to correct spinal deformities, joint problems, and airway obstructions.
• Physical therapy: Helps maintain mobility, strength, and flexibility.
• Respiratory care: Continuous monitoring and treatment of breathing problems, including CPAP therapy for sleep apnea.
• Hearing aids: For individuals with significant hearing loss.
• Regular monitoring: Cardiologic, orthopedic, and pulmonary assessments to manage associated complications.

Prognosis

The prognosis of Morquio Syndrome depends on the severity of the disease and the type (IVA or IVB). Early diagnosis and modern therapies like ERT have improved the outlook for many patients. While individuals with Morquio Syndrome face progressive physical challenges, many maintain normal cognitive abilities and can lead fulfilling lives with appropriate medical care and supportive therapies. Lifespan may be shortened in severe cases due to respiratory or cardiac complications, but proactive management can enhance life expectancy and overall well-being.