Morquio A Syndrome - A Congenital Metabolic Syndrome

What Is Morquio A Syndrome?

It is a rare, metabolic, and congenital disorder that impacts skeletal development. It is one of the 50 lysosomal storage disorders. In this disorder, the body cannot process specific sugar molecules (glycosaminoglycans). The Mucopolysaccharidosis type IV, when involved, induces skeletal manifestations that include abnormal spine curvature, short neck, knock knees, and hip issues. Affected children present with an enlarged head and characteristic facial features. Supportive measures aid in managing physical effects, but intellectual abilities remain unaffected. Morquio A Syndrome affects men and women equally. The syndrome has an incidence of developing in every two or three lakh births. Most patients do not survive beyond 20 years.

What Causes Morquio A Syndrome?

It is a genetic condition caused by a mutation leading to deficiency of the GALNS (N-acetylgalactosamine-6-sulfate sulfatase) and GLB1 (Galactosidase Beta 1) genes. Mutation of both these genes causes the development of identical diseases. These genes are responsible for producing enzymes that digest large sugar molecules. Type A disease is caused by GALNS gene mutation, whereas type B develops from GLB1 mutation.

Dysfunction of the digestive enzymes leads to glycosaminoglycan accumulation, such as keratan sulfate and chondroitin-6-sulfate buildup within lysozymes. Keratan sulfate is majorly produced and accumulates within the cartilage and extracellular matrix. It directly affects cartilage and bone development, resulting in systemic skeletal spondyloepiphyseal dysplasia. Consequently, it creates a hazardous environment that manifests more strongly in bone cells, resulting in several abnormalities. The pattern of inheritance for the syndrome is autosomal recessive (two copies of abnormal genes). If the child has one defective gene, they become carriers of the syndrome and do not exhibit any symptoms.

What Are the Symptoms of Morquio A Syndrome?

Morquio syndrome is a disorder of metabolic abnormalities manifesting a wide range of symptoms, The most common being skeletal defects. The skeletal symptoms are the early signs which manifest during early childhood. The symptoms are:

• Short Height: Irregularities in the epiphysis and long bone development cause growth delays in children.

• Knock Knees: The children with this condition will have knees closer.

• Hip Issues: As bone and related tissues are affected by the syndrome, it causes excessive mobility of hips, resulting in dislocation. Some patients can also develop arthritis (joint disorder).

• Hypermobility: Individuals with this syndrome can demonstrate excessive instability and mobility in wrists, knees, elbow, and other joints.

• Neck Problems: The main problem due to the syndrome is a hypoplasia of the odontoid bone in the neck. It causes instability and spinal cord compression, resulting in paralysis or death.

• Flat Feet: Flattening of feet could affect the individual's gait. There is an increased tendency to fall.

• Chest Deformity: Underdevelopment of the rib cage causes compression of the lungs and heart. Obstructive or restrictive lung leads to respiratory failure, which significantly increases morbidity.

• Growth Defects: Children with this defect exhibit normal limbs but an abnormally short trunk.

• Vertebrae Flattening: X-ray investigation of individuals affected by the syndrome reveals vertebrae significantly flattened than usual.

• Skull Enlargement: Individuals affected by the syndrome have skulls larger than average.

• Facial Characteristics: Individuals with the syndrome exhibit a small nose, prominent cheekbones, wide-set eyes, broad mouth, and abnormally large head.

• Hearing Problems: Some children may develop partial or complete loss of hearing ability.

• Eye Problems: Some children affected by the syndrome develop clouding over the cornea of the eyes.

• Dental Issues: Widely-spaced teeth and thinner-than-usual enamel are some of the dental manifestations of the syndrome.

• Organ Enlargement: The liver and spleen of the affected individuals may become enlarged than usual.

• Reduction of Lifespan: Children with severe Morquio syndrome will have pronounced symptoms. Therefore, the children will not survive past adolescence. However, children with mild cases can live into adulthood even if their lifespan is affected.

How Is Morquio A Syndrome Diagnosed?

Medical history and physical examination help suspect the disease in the child. Most newborns with the syndrome appear healthy at birth but have radiographic changes in the spine before clinical symptoms develop. Most children are undiagnosed until they are two or three years old and develop prominent skeletal dysplasia. Imaging studies like X-rays help the doctor analyze the syndrome's effect on bones and joints.

Analysis of urine helps with diagnosis. A higher amount of glycosaminoglycans in urine indicates Morquio syndrome. Keratan sulfate assay with mass spectrometry can also help screen the syndrome. Type A and B forms of the disease can be differentiated with the help of molecular testing of the respective genes.

Is There a Cure for Morquio A Syndrome?

The initial treatment includes the management of physical symptoms, which requires help from several medical specialties. The treatment includes:

• Decompression Surgery: Affected individuals commonly develop compression of the upper neck and base of the skull. Therefore, such individuals undergo decompression surgery to release pressure and improve stability.

• Cardiac Surgery: A narrow and hypoplastic rib cage compresses the heart. It is managed with the surgical placement of a prosthetic valve.

• Airway Procedure: Disturbances to the airway are the most severe complication of Morquio syndrome. If there are enlarged adenoids or tonsils, it is removed surgically.

• Corneal Replacement: Children who develop clouding in their eyes can undergo keratoplasty (corneal replacement).

• Hearing Loss Treatment: Hearing loss is a common symptom treated with hearing aids. Some require surgery to place ventilation and auditory tubes.

• Occupational Requirements: Most children with the syndrome have normal intelligence and do not require special classes. However, it is essential to seat the children in front rows. Progression of the condition causes skeletal impairments, which increases the necessity for using walking aids or wheelchairs.

• Enzyme Treatment: The syndrome can be treated with special medication for replacing the GALNS enzyme level intravenously.

• Supportive Measures: Joint pains are managed by giving non-steroidal anti-inflammatory drugs. Otolaryngology infections are treated with antibiotics.

• Genetic Counseling: Individuals with a family history of the disorder must undergo genetic testing and counseling. It helps identify the risk of transmission if the couple wants to have kids. Gene therapy is needed to reduce the risk of developing the syndrome in the fetus.

• Counseling: Affected children and their families require mental health counseling to cope with the disease.

Conclusion

Genetic disorders are a challenging disease to treat. Children suffering from Morquio A syndrome require comprehensive treatment, which includes supportive therapy, physiotherapy, and orthopedic interventions. However, there is no complete cure for Morquio A syndrome. Symptoms could be effectively managed with multispeciality treatment.