Morquio syndrome

Overview

Morquio syndrome, also known as Mucopolysaccharidosis type IV (MPS IV), is a rare inherited lysosomal storage disorder characterized by the body's inability to break down specific complex carbohydrates called glycosaminoglycans (GAGs), particularly keratan sulfate and chondroitin-6-sulfate. This leads to their accumulation in cells, resulting in progressive damage to bones, cartilage, and various organs.

Morquio syndrome is classified into two main subtypes based on the specific enzyme deficiency:

• MPS IV A (Morquio A): Caused by deficiency of the enzyme galactosamine-6-sulfatase (GALNS)

• MPS IV B (Morquio B): Caused by deficiency of the enzyme beta-galactosidase (GLB1)

Children with Morquio syndrome typically appear normal at birth, but symptoms begin to emerge within the first few years of life, leading to skeletal abnormalities, short stature, joint laxity, and potential organ involvement. Intelligence is usually unaffected, especially in Morquio A. The severity and progression of the disease vary among individuals.

Causes

Morquio syndrome is caused by mutations in the genes responsible for producing the enzymes needed to degrade glycosaminoglycans:

• MPS IV A: Mutations in the GALNS gene (galactosamine-6-sulfatase)

• MPS IV B: Mutations in the GLB1 gene (beta-galactosidase)

These mutations lead to a deficiency or absence of the respective enzyme, resulting in the accumulation of GAGs in lysosomes—the cellular structures responsible for breaking down waste products.

Morquio syndrome follows an autosomal recessive inheritance pattern, meaning a child must inherit one defective copy of the gene from each parent to develop the condition. Parents who carry only one mutated gene are asymptomatic carriers.

Symptoms

Symptoms of Morquio syndrome typically appear between ages 1 and 3 and progress over time. The severity and specific features can vary depending on whether the individual has type A or B, with type A generally being more severe.

Common Symptoms

• Short-trunk dwarfism (disproportionately short stature)

• Abnormal curvature of the spine (kyphosis or scoliosis)

• Joint hypermobility or laxity

• Genu valgum (knock knees)

• Pectus carinatum (pigeon chest)

• Enlarged head (macrocephaly) with a prominent forehead

• Hip dysplasia and frequent joint dislocations

• Coarse facial features (in some cases)

• Dental anomalies (small, widely spaced teeth)

Additional Complications

• Respiratory issues due to airway obstruction and chest wall deformities

• Hearing loss

• Corneal clouding leading to vision impairment

• Heart valve abnormalities

• Neck instability due to odontoid hypoplasia, increasing the risk of spinal cord compression

Cognitive development is typically normal, particularly in Morquio A, distinguishing it from some other mucopolysaccharidoses that affect mental function.

Diagnosis

Diagnosing Morquio syndrome involves a combination of clinical evaluation, biochemical testing, imaging, and genetic analysis.

Diagnostic Process

• Physical examination: Evaluation of growth patterns, skeletal abnormalities, and joint mobility

• Urine tests: Elevated levels of glycosaminoglycans (especially keratan sulfate) suggest a mucopolysaccharidosis

• Enzyme activity assays: Confirm deficiency of GALNS (Morquio A) or GLB1 (Morquio B) in white blood cells or fibroblasts

• Genetic testing: Identification of mutations in the GALNS or GLB1 genes provides definitive diagnosis

• Radiographic imaging: X-rays may show skeletal dysplasia, spinal abnormalities, and other bone-related signs

• MRI: Used to assess spinal cord compression or other neurological complications

Early diagnosis is essential for initiating timely interventions and improving outcomes.

Treatment

There is no cure for Morquio syndrome, but treatment focuses on managing symptoms, slowing disease progression, and improving quality of life. A multidisciplinary team approach is often required, involving geneticists, orthopedists, cardiologists, pulmonologists, and physical therapists.

1. Enzyme Replacement Therapy (ERT)

• Elosulfase alfa (Vimizim): Approved for Morquio A (MPS IV A), helps reduce GAG accumulation and improve endurance and mobility

• ERT is administered via weekly intravenous infusions and may not correct skeletal abnormalities but can improve respiratory and physical function

2. Surgical Interventions

• Spinal decompression for cervical spine instability

• Corrective surgery for hip dysplasia or leg deformities

• Adenoid or tonsil removal for airway obstruction

• Corneal transplants in severe vision impairment (rare)

3. Supportive Therapies

• Physical therapy and occupational therapy for maintaining mobility

• Respiratory therapy for breathing difficulties

• Hearing aids and speech therapy if hearing loss is present

• Orthotic devices for joint stability

4. Regular Monitoring

• Cardiac evaluations for heart valve abnormalities

• Pulmonary function tests

• Neurological assessments for spinal cord compression

Genetic counseling is recommended for affected families to understand inheritance patterns and discuss family planning options.

Prognosis

The prognosis of Morquio syndrome depends on the severity of the disease and the effectiveness of symptom management. With early intervention and ongoing care, many individuals can lead active lives, although mobility and independence may be limited in severe cases.

Key Prognostic Factors

• Type A is usually more severe than type B

• Progressive skeletal and respiratory complications can affect quality of life and lifespan

• ERT and surgical interventions can improve functional outcomes and prolong life expectancy

In severe untreated cases, complications such as spinal cord compression, respiratory failure, or cardiac issues can reduce life expectancy. However, with comprehensive care, many individuals with Morquio syndrome can live into adulthood and maintain functional independence to varying degrees.