Morquio syndrome, also known as mucopolysaccharidosis type IV (MPS IV), is a rare genetic disorder caused by the body’s inability to process certain complex sugar molecules. It affects an estimated 1 in 200,000 to 1 in 300,000 live births in the United States.
Understanding Morquio Syndrome
Morquio syndrome is a lysosomal storage disorder where the body cannot properly break down glycosaminoglycans (GAGs). These complex sugar molecules are essential components of connective tissues, including bone, cartilage, and cornea. When specific enzymes needed for their breakdown are deficient or absent, GAGs accumulate within cells, tissues, and organs, causing progressive damage.
The syndrome is categorized into two main types: Morquio A (MPS IVA) and Morquio B (MPS IVB). Morquio A results from a deficiency of the enzyme N-acetylgalactosamine-6-sulfatase (GALNS), leading to the accumulation of keratan sulfate and chondroitin-6-sulfate. Conversely, Morquio B is caused by a deficiency of beta-galactosidase, which primarily leads to the accumulation of keratan sulfate. While both types present with similar clinical features, Morquio B is generally considered to have milder symptoms.
Genetic Basis of Morquio Syndrome
Morquio syndrome is an autosomal recessive inherited disorder, meaning that an individual must inherit two copies of a defective gene, one from each parent, to develop the condition. Parents who carry one copy of the mutated gene are typically asymptomatic themselves but can pass the gene to their children. If both parents are carriers, there is a 25% chance with each pregnancy that their child will inherit two defective copies and be affected by Morquio syndrome.
The specific genes involved differ between the two types. Morquio A is caused by mutations in the GALNS gene, and Morquio B arises from mutations in the GLB1 gene. These genetic alterations prevent the respective enzymes from functioning correctly, leading to GAG accumulation.
Recognizing the Signs
Individuals with Morquio syndrome usually appear healthy at birth, with symptoms typically beginning to manifest between one and three years of age. The most prominent signs involve progressive skeletal abnormalities due to GAG accumulation in bones and cartilage. These include short stature, often characterized by a very short trunk, and deformities of the spine such as kyphoscoliosis. Other common skeletal features are a bell-shaped chest, pectus carinatum (a protruding breastbone), knock-knees, and unusually flexible joints.
A particularly significant skeletal concern is odontoid hypoplasia, where the peg-like bone stabilizing the head and neck connection is underdeveloped. This can lead to instability in the cervical vertebrae, potentially compressing the spinal cord and causing serious neurological issues. Beyond skeletal problems, individuals may experience respiratory difficulties from a narrowed airway or chest deformities, leading to frequent infections and sleep apnea. Cardiac involvement, such as heart valve abnormalities, and sensory impairments like cloudy corneas, vision loss, and hearing loss are also common manifestations.
Diagnosis and Management Approaches
Diagnosing Morquio syndrome typically begins with a clinical evaluation, where medical professionals assess the characteristic physical signs. This is often followed by urine tests to detect elevated levels of GAGs, particularly keratan sulfate. Enzyme activity assays are then performed to measure the levels of the specific deficient enzymes, N-acetylgalactosamine-6-sulfatase or beta-galactosidase, confirming the diagnosis and identifying the type of Morquio syndrome. Genetic testing can provide definitive confirmation by identifying mutations in the GALNS or GLB1 genes.
Management of Morquio syndrome focuses on addressing symptoms and improving the individual’s quality of life, as there is currently no cure. For Morquio A, enzyme replacement therapy (ERT) with elosulfase alfa (Vimizim) is an approved treatment that involves regular intravenous infusions of the missing enzyme. This therapy can help reduce GAG accumulation and improve many symptoms, particularly in soft tissues. Orthopedic interventions, including bracing and surgeries like spinal fusion or joint replacement, are frequently necessary to manage skeletal deformities and prevent complications such as spinal cord compression. Multidisciplinary supportive care, involving respiratory support, physical therapy, and ongoing monitoring of cardiac and sensory functions, is crucial for comprehensive management.
Living with Morquio Syndrome
While intelligence is typically normal, the physical challenges of Morquio syndrome can significantly impact daily life. Ongoing medical care and consistent, multidisciplinary management are important for optimizing outcomes and improving quality of life for affected individuals.
The long-term outlook for individuals with Morquio syndrome varies depending on the specific type and severity of the condition. Individuals with more severe forms, particularly Morquio A, may have a reduced lifespan, often into their twenties or thirties, with respiratory failure and cardiac complications being common causes of mortality. Despite these challenges, advancements in medical care continue to improve the prognosis and daily realities for those living with Morquio syndrome.