About Morquio Syndrome

Morquio syndrome follows an autosomal recessive inheritance pattern.⁹

A mutation is the GALNS gene, which encodes for N-acetyl galactosamine-6-sulfatase, causes Morquio, type A.⁴ Type B is caused by mutations of the GLB1 gene, which encodes for β-galactosidase.⁴ Both enzymes, however, are responsible for keratan sulfate degradation. In type A, the activity of the sulfatase was found to be less than 1%.⁶ Due to the enzymes’ ineffectiveness, mucopolysaccharides aggregate within intracellular lysosomes. Mucopolysaccharides are long, unbranched chains of repeating saccharide, or sugar, units. They are important components of the body’s connective tissues and are often times covalently linked to proteins.

In Morquio syndrome, the lysosomal enzymes that are responsible for breaking down mucopolysaccharides are ineffective. As a result, the long sugar molecules begin to collect in the body’s cells and connective tissues. The accumulation ultimately causes cellular damage that manifests as skeletal malformations.

Face and Skull

• Mildly coarse facial features
• Accentuated lower portion of the face
• Broad mouth
• Short anteverted nose
• Corneas of the eyes become cloudy
• Widely spaced teeth
• Hypoplasia of tooth enamel

Trunk, Chest and Spine

• Barrel-shaped chest
• Flaring lower rib cage
• Prominent sternum (pectus carinatum)
• Stunted neck and trunk
• Considerably short spine marked platyspondyly (flattened vertebral bodies)

Arms and Legs

• Severe flexion deformities of the limbs
• Ligamentous laxity, especially at the wrists and small joints
• Joint restriction prominent at the larger joints, most notably at the hips
• Awkward gait
• Knock-knees
• Flat feet
• Prominent buttocks
• Short and stubby hands
   

X-Ray Characteristics

The major radiographic features of Morquio syndrome include marked platyspondyly in the thoracic and lumbar spine. The shape of the vertebrae change from ovoid, to ovoid with anterior projection, to flat.

Odontoid hypoplasia with atlantoaxial instability is typical. Thoracolumbar kyphosis can develop over time and can result in spinal cord compression. The skull is mildly dolichocephalic (elongated) with underdevelopment of mastoid cells and flat or concave mandibular condyles. 

A flaring lower rib cage with pectus carinatum is typical of the thorax. A premature fusion of the ossification centers of the sternum usually occurs. 

The long bones are short and curved, with irregular tubulation. Metaphyses are irregularly wide. Ossification centers tend to develop slowly. Coxa valga is characteristic, along with an abnormal femoral neck and flattening of the femoral head.

Genu Valgus and a medial spur of tibial metaphysis are often times seen. The bases of the second through fifth metacarpals are conically shaped. The feet have irregular contour with delayed ossification of the tarsal bones. There is central constriction and general shortness of the metacarpals and phalanges.

Morquio Syndrome is typically not recognized at birth. Signs are not typically recognized until the second to fourth year of life and are most frequently gait disturbance and/or growth deficiency.

When there is suspicion of Morquio syndrome, laboratory evaluation include testing for keratin sulfate accumulation in the urine and measuring enzyme activity in white blood cells. Confirmation of the diagnosis can be completed through genetic testing. 

Prenatal recognition can be done using amniotic fluid cells and chorionic villi.

Spine

Children with Morquio syndrome can have several concerns with their spine, including instability and stenosis (or tightness), that can result in spinal cord compression and permanent injury. It is recommended that all children receive an MRI of their spine when they are diagnosed with Morquio syndrome, and then at routine Intervals thereafter. Whenever they will be sedated for a procedure lasting longer than 60 minutes, families should discuss the need for neuromonitoring with their physician, which keeps patients safe with  continuous observation of the spinal cord. 

Upper cervical spine instability along with compression of the spinal cord is a serious complication that can occur at any age in Morquio syndrome. Annual xrays and physical exam, followed by MRI as needed, are essential to ensuring the safety of patients. If left untreated, spinal cord compression can result in loss of the ability to breathe or walk unassisted. Early symptoms of spinal cord compression include tingling or numbness in the arms or legs, muscle weakness, or changes in the function of the sphincters of the bowels and bladder. Treatment requires surgery to decompress the bone around the spinal cord, followed by instrumentation of the bone with metals implants to allow it to fuse. 

Patients may also develop a kyphosis, or curvature, lower in the thoracolumbar spine. Kyphosis can be progressive and become very stiff, causing patients to lean forward, and develop some low back pain. Kyphosis may also result in spinal cord compression, with symptoms as listed above. Concern for progressive kyphosis with symptoms requires an examination, x-rays and an MRI. Again, treatment requires surgical decompression and fusion of the spine. 

Upper Limbs

Ligamentous laxity is progressive and significant especially of the wrists and ankles. The force able to be delivered by the long flexors of the fingers and thumbs becomes considerably weak. The wrists may need to be stabilized, which will help to increase the effectiveness of the muscles and to improve function. Wrist fusions have been attempted; however, most attempts have failed.

Hips

Children with Morquio syndrome are born with well-formed hips, but progression of the disease in childhood results in femoral head flattening and widening, or subluxation, of the hips. This can progress to complete hip dislocation and result in degenerative osteoarthritis with hip pain and a decline in walking. Osteoarthritis can be delayed with hip reconstruction between 5-10 years old, reseating and stabilizing the hips. When osteoarthritis results in daily hip pain and limitations, many patients benefit from total hip replacement. 

Lower Limbs

Knock -knee deformity (genu valgum) classically begins in toddlers, and often progresses with the child’s growth. Both bony changes and ligamentous laxity contribute to genu valgum . In severe cases, the knock-knee may interfere with ambulation. Before the age of 10, many children’s knees are corrected with guide-growth. Typically, the correction is long-lasting once the patient reaches skeletal maturity between 10-12 years of age. After skeletal maturity, it is still possible to correct genu valgum with an osteotomy. 

Respiratory

By late teens and adulthood, the ribs are nearly horizontal and the sagittal diameter of the chest is greater than average. As a result, respiratory expansion becomes considerably impaired. Moreover, frequent upper and lower respiratory tract infections may occur due to the malformation of the rib cage. 

Over half of people with Morquio syndrome develop narrowing of their trachea in the second decade of life. This can lead to life-threatening complications, especially during anesthesia. Therefore, imaging of the airway is recommended towards the end of the first decade as well as prior to any surgery thereafter. Treatment with surgery to reconstruct the trachea can be necessary in severe cases.

Lung function tests and sleep studies are frequently used to diagnose breathing problems in skeletal dysplasias. Regular visits with a pulmonologist is recommended. In the setting of prolonged severe breathing difficulties, some patients/families may choose invasive respiratory support with a tracheostomy and long-term mechanical ventilation.

Cardiac

Cardiac complications may occur, including cardiomyopathy, valvular disease or a late onset of aortic regurgitation. Cardiac anomalies are predominately left sided. Severe cases have resulted in death before the age of 20. Regular echocardiograms can be helpful in detecting concerns early and intervening when possible. 

Abdomen

Enlargement of the liver and the spleen is common in Morquio. This is typically lessened with the use of enzyme replacement therapy (ERT). Despite enlargement, function is not compromised. Inguinal hernias can also be seen. 

Ears

Conductive hearing loss, due to the accumulation of fluid behind the ear drum, can be seen. Myringotomy tubes are typically helpful for this; however, at times, hearing aids are required. 

Eyes

Corneal clouding is typical once patients reach age 5. Glaucoma of the eyes and pigmentary retinal degeneration may occur in older patients. Ophthalmologic examination is needed at frequent intervals.

Skin

Cutaneous abnormalities may also be present, including loose, thickened, tough and inelastic skin, particularly of the extremities. Generalized telangiectasia of the face and limbs has also been reported.

Teeth

Appropriate dental care is required due to the hypoplasia of tooth enamel. Teeth often brown and discolor easily. The permanent posterior teeth have pointed cusps; there is often times pitting of the buccal surfaces. The teeth are also widely spaced.

Mental Capacity

Intelligence and mentality is typically not impaired in Morquio type A. However, progressive mental deficiency does occur in Morquio Type B.

Enzyme Replacement Therapy (ERT)

Monitoring

Although the first 18 months are characterized by relatively typical development, beyond this age, Morquio patients tend to decline, especially in proportionate growth and mobility.

Any change in walking ability, endurance or breathing merits further assessment by a physician to rule out spinal cord compression. Specific neurological symptoms such as tingling or numbness in the arms or legs, weakness, shooting leg or arm pain, or problems controlling bladder/bowel function should be investigated further.

Considering that eye and teeth problems are especially associated with Morquio syndrome, ophthalmologic consultation and dental examinations are recommended for early detection and treatment.

Generally, all skeletal dysplasias warrant multidisciplinary attention. Regular assessment by an orthopedist, geneticist, pediatrician, dentist, neurologist and physical therapist will provide the most comprehensive treatment.

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