Morquio syndrome, type A or MPS IVA is a metabolic condition that primarily affects the skeleton. The severity, age of onset, and associated symptoms vary significantly from person to person and range from a severe and rapidly progressive, early-onset form to a slowly progressive, later-onset form. The severe form is usually diagnosed between ages 1 and 3, while the milder form may not become evident until late childhood or adolescence. MPS IVA is caused by mutations in the GALNS gene and is inherited in an autosomal recessive manner. Treatment is based on the signs and symptoms present in each person.
Possible symptoms may include:
- Abnormality of the heart valves
- Cervical myelopathy
- Cervical subluxation
- Chondroitin sulfate excretion in urine
- Coarse facial features
- Constricted iliac wings
- Coxa valga
- Disproportionate short-trunk short stature
- Epiphyseal deformities of tubular bones
The first signs and symptoms are usually become apparent during early childhood. Affected individuals develop various skeletal abnormalities, including short stature, knock knees, and abnormalities of the ribs, chest, spine, hips, and wrists. People with MPS IV often have joints that are loose and very flexible (hypermobile), but they may also have restricted movement in certain joints. A characteristic feature of this condition is underdevelopment (hypoplasia) of a peg-like bone in the neck called the odontoid process. The odontoid process helps stabilize the spinal bones in the neck (cervical vertebrae). Odontoid hypoplasia can lead to misalignment of the cervical vertebrae, which may compress and damage the spinal cord, resulting in paralysis or death.
Mutations in the GALNS and GLB1 genes cause MPS IV. These genes provide instructions for producing enzymes involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). GAGs were originally called mucopolysaccharides, which is where this condition gets its name. When MPS IV is caused by mutations in the GALNS gene it is called MPS IV type A (MPS IVA), and when it is caused by mutations in the GLB1 gene it is called MPS IV type B (MPS IVB). In general, the two types of MPS IV cannot be distinguished by their signs and symptoms.
Morquio syndrome is transmitted through generations as an autosomal recessive trait. It has several symptoms in common with other mucopolysaccharide storage diseases such as coarse facial features, short stature, and skeletal and joint abnormalities. Like Sanfilippo syndrome, onset of symptoms is delayed until after the first year, and life expectancy may exceed 20 years. Unlike Sanfilippo syndrome, the mental development is often normal.
Genetic counseling is recommended for prospective parents with a family history of Morquio syndrome.
- X-ray of the long bones
- X-ray of the ribs
- X-ray of the spine shows abnormal vertebrae and osteoporosis
- Urine chemistry, keratosulfate or chondroitin sulfate may be increased
- Culture of skin fibroblasts or white blood cells for deficient galactosamine-6-sulfatase or beta galactosidase enzyme activity
- Hearing test
- Slit-lamp eye exam for abnormal deposits in cornea
- Echocardiogram may show thickened heart valves
- Genetic testing may be available
Bone abnormalities represent a significant problem, and correction through surgery should be made where possible. For example, small vertebrae at the top of the neck can cause slippage that damages the spinal cord so that paralysis may result. Death may occur as a result of cardiac complications
elosulfase alfa (Vimizim) - FDAapproved indication: Patients with Mucopolysaccharidosis type IVA Morquio A syndrome)