User:SaswatPanda/Osteochondrodystrophia Deformans

Morquio's syndrome (referred to as mucopolysaccharidosis IV or Morquio's) is an autosomal recessive mucopolysaccharide storage disease (see also lysosomal storage disorder), usually inherited. It is a rare type of birth defect with serious consequences. When the body cannot process certain types of mucopolysaccharides, they build up or are eliminated, causing various symptoms. These involve accumulation of keratan sulfate. Although Morquio's is typically associated with dwarfism, it is a metabolic disorder which affects lysosomal storage. Individuals with Morquio's have a deficiency of N-acetylgalactosamine-6-sulfatase (GALNS, EC 3.1.6.4; encoded by GALNS gene at 16q24.3).

History
The condition was first described, simultaneously and independently, in 1929, by Luis Morquio (1867–1935), a well-known Uruguayan physician who discovered it in Montevideo, and James Frederick Brailsford (1888–1961), an English radiographer in Birmingham, England.

They both recognized the occurrence of corneal clouding, aortic valve disease, and urinary excretion of keratan sulfate. Morquio observed the disorder in four siblings in a family of Swedish extraction and reported his observations in French. The chances of getting Morquio is 1 in 200,000. The estimated incidence of Morquio B ranges from around 1 case per 75,000 births in Northern Ireland to 1 case per 640,000 births in Western Australia.

Interventions
As Morquio can cause spinal cord compression, it has long been treated surgically, through different techniques for decompressing the spine such as spinal fusion

The other symptoms of Morquio have been treated using substrate reduction therapy, to reduce the build up of keratan sulfate which is associated with the disease, using a drug called N-butyldeoxynojirimycin (NB-DNJ or Miglustat). Currently Miglustat is primarily used to treat Gaucher Disease, Niemann-Pick disease and chronic GM2 glandliosidosis type Sandhoff.

Symptoms
The following symptoms are associated with Morquio's syndrome:


 * Abnormal heart development
 * Abnormal skeletal development
 * Hypermobile joints
 * Large fingers
 * Knock-knees
 * Widely spaced teeth
 * Bell-shaped chest (flared ribs)
 * Compression of spinal cord
 * Enlarged heart
 * Dwarfism
 * Heart Murmur

Patients with Morquio's syndrome appear healthy at birth. They are often present with spinal deformity, and there is growth retardation and possibly genu valgum in the second or third year of life. A patient with Morquio's syndrome is likely to die at an early age. Other symptoms of the disease may include:


 * Short stature and short neck (caused by flat vertebrae)
 * Moderate kyphosis or scoliosis
 * Mild pectus carinatum ("pigeon chest")
 * Cervical spine: odontoid hypoplasia, atlanto-axial instability; may be associated with myelopathy with gradual loss of walking ability
 * Joint laxity, mild dysostosis multiplex, dysplastic hips, large unstable knees, large elbows and wrists, and flat feet
 * The combined abnormalities usually result in a duck-waddling gait
 * Mid-face hypoplasia and mandibular protrusion
 * Thin tooth enamel
 * Corneal clouding
 * Mild hepatosplenomegaly

Life span: some can die as early as 2 or 3 and some can live up to 60 or 70 years old.

Current Research
Current research regarding Morquio's primarily pertains to enzyme replacement therapy (ERT) and trials for hematopoetietic stem cell transplantation (HSCT) are also being done.

Radiology Features

 * Skull
 * macrocephaly,
 * a thickened vault with ‘ground-glass’ opacity
 * ‘J’-shaped sella, elongated


 * Vertebrae
 * Anterior lower vertebral body central ‘beak’
 * an absent odontoid peg (with associated cervical instability leading to spinal cord compression)
 * platyspondyly (flattened vertebral bodies)
 * hookshaped vertebral bodies with a thoracolumbar gibbus


 * Limbs
 * short stature
 * lack of normal modelling of the long bones(with thin cortices and a coarse trabecular pattern)
 * short wide phalanges with a characteristic proximal pointing of the metacarpals
 * joint laxity
 * delayed appearance of fragmented stippled epiphyses
 * proximal pointing of the 2nd to 5th metacarpals
 * Anterior central vertebral body ‘beak’


 * Chest radiograph
 * broad wide ribs,
 * short broad wide clavicles and
 * poorly modelled scapulae


 * Pelvis
 * The iliac wings are flared laterally with constricted bases to the iliac bones (‘goblet shaped’ or‘wineglass’ pelvis)
 * The acetabular roofs are shallow. Bilateral hip subluxation with long femoral necks
 * coxa valga
 * small, irregular femoral capital epiphyses

Treatment
The treatment for Morquio's syndrome consists of prenatal identification and of enzyme replacement therapy. On 12 February 2014, the Federal Drug Administration approved the drug elosulfase alfa (Vimizim) treating the disease.