Morquio Syndrome (MPS IV) is an inherited metabolic disorder classified as a lysosomal storage disease. It is caused by the body’s inability to break down specific complex sugar molecules called glycosaminoglycans (GAGs). These GAGs, which are involved in building bone, cartilage, and connective tissues, accumulate within the cells’ lysosomes due to a lack of specific enzymes, leading to progressive cellular damage. The syndrome has two primary types. Morquio A (Type IVA) accounts for about 95% of cases and involves a deficiency of the enzyme N-acetylgalactosamine-6-sulfatase (GALNS). Morquio B (Type IVB) is less common and is caused by a lack of beta-galactosidase (GLB1). Both types result in the buildup of Keratan Sulfate, impacting the structure and function of multiple organ systems.
Understanding the Onset of Morquio Syndrome
Infants with Morquio Syndrome appear healthy at birth because GAG accumulation has not yet caused external signs. Initial symptoms typically manifest between one and three years of age, often coinciding with the achievement of motor milestones. Parents may first notice a failure to thrive or a deceleration in growth as skeletal abnormalities begin to interfere with typical development.
One of the earliest indicators is a distinctive waddling or abnormal gait, linked to early hip and leg deformities. As the child grows, the disproportionate effect on the spine and trunk becomes more apparent, setting the stage for defining physical characteristics later in early childhood.
Defining Characteristics: Skeletal and Joint Abnormalities
The most recognizable signs of Morquio Syndrome are widespread skeletal abnormalities, known as systemic skeletal dysplasia. This results in distinctive short-trunk dwarfism, where the torso is disproportionately short compared to the limbs, leading to reduced overall height. Physical growth often slows significantly or stops entirely by around eight years of age.
Specific spinal issues are a major concern, most notably the underdevelopment of the odontoid process (C2). This condition, known as odontoid hypoplasia, causes severe instability at the skull and spine junction, posing a serious risk for spinal cord compression and neurological damage. Spinal curvatures are also common, including kyphosis (excessive outward curvature) and scoliosis (sideways curvature).
The chest wall is frequently affected, leading to pectus carinatum, or “pigeon chest,” where the sternum protrudes outward. This abnormality, combined with a short neck and flaring ribs, restricts the chest cavity volume, contributing to later respiratory difficulties. Lower extremities often exhibit genu valgum, commonly known as knock-knees, where the knees angle inward.
Paradoxically, while the skeletal structure is malformed, the joints are often hypermobile due to ligamentous laxity. This excessive joint movement, noticeable in the wrists, ankles, and hips, eventually leads to pain, joint degeneration, and limited range of motion. The combination of hip dysplasia, knock-knees, and joint laxity contributes significantly to the abnormal gait and the need for mobility assistance. Many patients also develop coarse facial features, including a broad mouth, a flattened nasal bridge, and widely spaced teeth.
Impact on Internal Systems: Sensory, Respiratory, and Cardiac Issues
GAG accumulation affects soft tissues and internal organs, leading to significant systemic complications beyond the skeleton. Vision is often compromised by corneal clouding (opacity), caused by Keratan Sulfate buildup within the cornea’s layers, though cognitive function is typically preserved as the central nervous system is generally spared.
Hearing loss is a frequent sensory issue, presenting as conductive, sensorineural, or mixed forms. Conductive loss is often due to skeletal abnormalities in the middle ear or chronic infections, while sensorineural loss relates to inner ear damage. These deficits necessitate early and ongoing monitoring.
Respiratory function is challenged by the restricted chest cavity resulting from skeletal and spinal deformities. This structural restriction makes breathing less efficient, often compounded by GAG deposition causing thickening of the trachea and upper airway walls. Obstructive sleep apnea is a common complication arising from airway narrowing and instability.
The heart is a major site of GAG accumulation, primarily affecting the valves. Thickening of the mitral and aortic valves (valvular heart disease) can lead to heart murmurs and compromise the heart’s ability to pump blood effectively. Some individuals may also exhibit an enlarged liver (hepatomegaly) due to the generalized storage of complex sugars.
Confirming the Condition: Diagnostic Procedures
When physical signs like growth deficiency and skeletal abnormalities prompt suspicion, clinicians initiate a diagnostic process. The first laboratory evaluation is typically a urine test, which measures GAG levels, specifically looking for high concentrations of Keratan Sulfate. Excessive GAGs suggest a lysosomal storage disorder, but not specifically Morquio Syndrome.
To pinpoint the exact disorder, an enzyme assay is performed to measure the activity of the deficient enzymes. For Morquio A, the assay tests for N-acetylgalactosamine-6-sulfatase (GALNS) activity, and for Morquio B, it tests for beta-galactosidase (GLB1) activity. Reduced or absent enzyme activity confirms the biochemical diagnosis.
Genetic testing provides definitive confirmation by analyzing the patient’s DNA for mutations in the GALNS or GLB1 genes. This identifies the specific type of Morquio Syndrome, which guides prognosis and treatment. Imaging studies, including X-rays and MRI, are used to visualize the extent of skeletal damage, confirm odontoid hypoplasia, and assess the risk of spinal cord compression.