Morquio syndrome is a genetic disorder.

Morquio syndrome is a genetic disorder

    Rare disease

Morquio syndrome?

Morquio syndrome, also called mucopolysaccharidosis type IV (MPS IV), is a rare genetic disorder that impacts how the body breaks down glycosaminoglycans. Usually, affected children live to adulthood with a normal IQ. The enzyme deficit distinguishes two forms:

Types and Causes

A lack of GAG-degrading enzymes causes this lysosomal storage disease.

Two types:

• Type A: Galactosamine-6-sulfatase deficiency.
• Type B: GLB1 deficiency.
• A child must inherit the gene from both parents because it is autosomal recessive.

Commonness of Morquio syndrome? (Epidemiology)

Diagnostic procedures, genetic factors, and population size affect Morquio syndrome (MPS IV), which is ultra-rare.

Prevalence Estimation Challenges

• Underdiagnosis: Other skeletal ailments may cause symptoms.
• Different countries utilize different diagnostic methods and criteria.
• Genetic diversity: Consanguinity and founder factors affect local occurrence.
• Data collection and quality standards are inconsistent in many studies.

Present Morquio's syndrome symptoms

Morquio syndrome (MPS IV) symptoms appear between 1 and 3 and worsen over time. The illness mostly affects the skeleton, but other organs and systems may be implicated.

• Physical Body Features
• Short stature, short trunk
• Curvature of the spine
• Bell-shaped chest, flaring ribs
• Valgum knock-knees
• Extremely movable knees and wrists

Underdeveloped cervical vertebrae (odontoid hypoplasia) 

• Increase spinal cord compression risk.
• Big head, low nasal bridge, widely spaced teeth
• Facial and sensory involvement
• Cloudy corneas impede vision
• Recurrent ear infections cause hearing loss.
• Teeth abnormalities: weak enamel, delayed eruption

Symptoms of Organs and Systems

• Sleep apnea, airway blockage, frequent infections
• Cardiovascular issues: valve abnormalities
• Liver enlargement
• Internal/umbilical hernias

Neurological Risks

• Paralysis or weakness can result from spinal cord compression.
• The patient maintains normal intelligence until the onset of hydrocephalus.

Investigations and differential diagnosis

This systematic summary of Morquio syndrome (MPS IV) differential diagnosis and studies can assist in distinguishing it from other skeletal and metabolic disorders:

• Differential diagnosis

Many disorders, including skeletal dysplasia and mucopolysaccharidoses, resemble Morquio's syndrome. Differences include:

🧬 Other MPS Conditions

• Hurler syndrome (MPS I-H) exhibits more severe CNS involvement and anteroinferior vertebral beaking.
• Hunter syndrome (MPS II): X-linked, no corneal clouding.
• Neurological symptoms dominate Sanfilippo syndrome (MPS III).
• Maroteaux-Lamy syndrome (MPS VI) exhibits similar skeletal characteristics and a distinct enzyme deficit.
• Sly syndrome (MPS VII): Skeletal-organ overlap.

Bone Dysplasia

• Spondyloepiphyseal dysplasia involves short height, spinal abnormalities, and little GAG buildup.
• Despite radiographic similarities, SMD commonly causes intellectual impairment. — Dyggve-Melchior-Clausen syndrome (DMC): Intellectual impairment and iliac crest abnormalities.
• Smith-McCort syndrome (SMC) is characterized by normal intelligence and a similar skeletal structure.
• Legg-Calvé-Perthes disease (LCPD) typically causes unilateral femoral head necrosis.

🧠 Other Conditions

• Juvenile or late-onset GM1 gangliosidosis may be associated with neuronopathic Morquio B.
• Achondroplasia: Short stature without systemic involvement.
• The condition manifests as poor bone health, blue sclerae, and hearing loss.

Also read https://biomarin.eu/our-motivation/diseases-and-conditions/morquio-a-syndrome/.

Investigations

Multiple tests are used to confirm Morquio's syndrome and rule out differentials:

Biochemical tests

• GAG testing in urine: High keratan sulfate.
• Assays of enzymes
• Type A: Galactosamine-6-sulfatase shortage.
• Beta-galactosidase deficiency (GLB1)

A genetic test

• GALNS or GLB1 genes undergo molecular analysis to facilitate subtyping and therapy.

Imaging Studies

• X-rays: Central vertebral body beaking, platyspondyly, flaring iliac wings, and coxa valga.
• MRI/CT: Check odontoid hypoplasia and spinal cord compression.
• Echocardiography: Assess heart valve issues.

In Ophthalmology, 

• A slit-lamp exam can detect corneal clouding.

Neurological Evaluation

• When compression or instability occurs, spinal cord function tests are important.

Management of Morquio syndrome

The video about the Enzyme treatment for children with Morquio syndrome 

Morquio syndrome (MPS IV) requires comprehensive treatment to reduce symptoms, preserve function, and improve quality of life. There's no cure, but numerous methods can halt advancement and support daily life.

• Enzyme replacement therapy (ERT) using elosulfase alfa (Vimizim) is authorized for Morquio A (MPS IVA).
• Reduces glycosaminoglycan (GAG) accumulation with weekly IV infusions.
• It enhances endurance and respiratory function, but it does not contribute to bone repair.

Management of Pain:

• Take NSAIDs or other medications for joint/skeletal pain.
• Reduce stiffness and increase mobility with physical therapy.

Supporting respiration:

• Use BIPAP or CPAP to treat sleep apnea.
• Remove tonsils/adenoids or perform a tracheostomy for severe airway obstruction.

Surgical Interventions

• In orthopedic surgery, spinal decompression is used to relieve cord compression.
• Scoliosis, knock-knees, and hip dysplasia surgery.
• In cardiac surgery, valve repair or replacement may be necessary due to extensive heart involvement.
• Ophthalmologic Surgery: Corneal transplant for severe clouding.

There is supportive and rehabilitative care.

• Physical and Occupational Therapy: Customized regimens for joint function and independence.
• Wheelchairs, braces, and walkers.

Hearing and Vision Aids:

• Hearing aids or ventilation tubes for recurring ear infections.
• Regular eye exams and glasses.

Support psychosocial:

• Emotional counseling.
• Help with school and social integration.

Long-term management

• Regular Monitoring: Annual cardiac, respiratory, orthopedic, and neurological evaluations.
• Imaging (MRI, X-rays) for skeletal progression.

Genetic Counseling:

• To educate impacted families about inheritance and reproduction.
• The multidisciplinary team includes geneticists, orthopedists, cardiologists, pulmonologists, ENT experts, and therapists.

Complications

Many problems of Morquio syndrome (MPS IV) result from growing skeletal abnormalities and organ involvement. These consequences range in severity and can compromise mobility, breathing, and quality of life.

🧠 Major Complications:

•  Neurological Spinal cord compression from odontoid hypoplasia or cervical instability.
• Untreated limb paralysis or weakening may occur. Hydrocephalus is infrequent but possible.
• The respiratory system may be affected by airway blockage caused by skeletal disorders.
• Sleep apnea, chronic respiratory infections
• Limited lung capacity from chest deformity

❤️ Cardiovascular:

• Abnormal heart valves, particularly mitral and aortic valves.
• Advanced cardiac failure

• Skeletal

• Kyphosis or severe scoliosis
• Knock-knees, hip dysplasia, joint instability
• Early-onset arthritis and persistent discomfort

• Sensory

• Loss of vision from cloudy corneas
• Recurrent ear infections or ossicular chain anomalies cause hearing loss.

Systemic hepatomegaly (enlarged liver)

• Internal/umbilical hernias
• Insufficient enamel, delayed eruption

Long-term results

• Reduced mobility: Many adolescents and adults need wheelchairs.
• Respiratory or cardiac failure can kill in the 20s–30s in severe circumstances.
• Unless hydrocephalus is untreated, intellect is normal.

Prognosis

Morquio syndrome (MPS IV) prognosis varies depending on type (A or B), intensity of symptoms, and timing and quality of medical therapies. A breakdown:

Overview of General Prognosis

• Progressive disease: Skeletal and respiratory symptoms intensify.
• Except for hydrocephalus, cognitive function is usually unaltered.
• Mobility decline: By adolescence or early adulthood, many people use wheelchairs.

Type-based prognosis:

• Enzyme Deficiency, Life Expectancy by Severity
• MPS IVA GALNS More severe. Good care can extend life into the 20s–30s or 50s–60s.
• MPS IVB-GLB1  Milder: May live into middle adulthood or longer. Prognostic Factors
• Untreated spinal cord compression can cause paralysis or death.
• The common cause of death owing to chest abnormalities and airway obstruction is respiratory failure.
• Valve disease can cause heart failure.
• Access to care: Type A enzyme therapy, early diagnosis, and surgery improve results.

A Long-Term View

• Many people with physical impairments can live fulfilled lives with multidisciplinary care.
• Despite slowing Type A progression, enzyme replacement therapy does not repair bone damage.
• In odontoid hypoplasia, cervical vertebrae fusion can save lives.

Conclusion.

Morquio syndrome (MPS IV) is an uncommon, inherited metabolic disorder that causes progressive skeletal defects, respiratory issues, and organ involvement. Intelligence is usually intact. Enzyme replacement therapy, surgery, and multidisciplinary care can improve quality of life and survival, especially in Type B cases, though there is no cure. Proactive diagnosis and management reduce problems and support long-term function.