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.^[1] 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.^[2] 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).^[3] ^[4]

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.^[5]^[6]^[7]

They both recognized the occurrence of corneal clouding, aortic valve disease, and urinary excretion of keratan sulfate.^[8] 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.^[9]^[10]

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^[11]^[12]^[13]

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. ^[14]^[15]^[16]

Symptoms

The following symptoms are associated with Morquio's syndrome:

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.^[17]^[18]

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.^[19]

References

^ James, William D.; Berger, Timothy G. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. {{cite book}}: Invalid |display-authors=3 (help)
^ Prat C, Lemaire O, Bret J, Zabraniecki L, Fournié B (May 2008). "Morquio syndrome: Diagnosis in an adult". Joint Bone Spine. 75 (4): 495–8. doi:10.1016/j.jbspin.2007.07.021. PMID 18456538.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Davison, J. E., Kearney, S., Horton, J., Foster, K., Peet, A. C., & Hendriksz, C. J. (2013). Intellectual and neurological functioning in Morquio syndrome (MPS IVa). Journal of inherited metabolic disease, 36(2), 323-328.
^ Northover, H., Cowie, R. A., & Wraith, J. E. (1996). Mucopolysaccharidosis type IVA (Morquio syndrome): a clinical review. Journal of inherited metabolic disease, 19(3), 357-365.
^ synd/2108 at Who Named It?
^ Morquio, L. (1929). "Sur une forme de dystrophie osseuse familiale". Archives de médecine des infants. 32. Paris: 129–135. ISSN 0365-4311.
^ Brailsford, J. F. (1929). "Chondro-osteo-dystrophy: Roentgenographic & clinical features of a child with dislocation of vertebrae". American Journal of Surgery. 7 (3). New York: 404–410. doi:10.1016/S0002-9610(29)90496-7.
^ Y. Suzuki, A. Oshima, E. Namba β-Galactosidase deficiency (β-galactosidosis) GM1 gangliosidosis and Morquio B disease C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle (Eds.), The Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill, New York (2001), pp. 3775–3809
^ Nelson, J. (1997). Incidence of the mucopolysaccharidoses in Northern Ireland. Human genetics, 101(3), 355-358.
^ J. Nelson, J. Crowhurst, B. Carey, L. Greed Incidence of the mucopolysaccharidoses in Western Australia Am. J. Med. Genet. A, 123A (2003), pp. 310–313
^ Borlot, F., Arantes, P. R., Cardoso, A. C. C., & Kim, C. A. (2014). Remote spinal cord injury in mucopolysaccharidosis type IVA after cervical decompression. Neurology, 82(15), 1382-1383.
^ Montano, A. M., Tomatsu, S., Gottesman, G. S., Smith, M., & Orii, T. (2007). International Morquio A Registry: clinical manifestation and natural course of Morquio A disease. Journal of inherited metabolic disease, 30(2), 165-174.
^ Blaw, M. E., & Langer, L. O. (1969). Spinal cord compression in Morquio-Brailsford's disease. The Journal of pediatrics, 74(4), 593-600.
^ P. Giraldo, P. Alfonso, K. Atutxa, M.A. Fernández-Galán, A. Barez, R. Franco, D. Alonso, A. Martin, P. Latre, M. Pocovi Real-world clinical experience with long-term miglustat maintenance therapy in type 1 Gaucher disease: the ZAGAL project Haematologica, 94 (2009), pp. 1771–1775
^ M. Pineda, M.S. Perez-Poyato, M. O'Callaghan, M.A. Vilaseca, M. Pocovi, R. Domingo, L.R. Portal, A.V. Pérez, T. Temudo, A. Gaspar, J.J. Peñas, S. Roldán, L.M. Fumero, O.B. de la Barca, M.T. Silva, J. Macías-Vidal, M.J. Coll Clinical experience with miglustat therapy in pediatric patients with Niemann–Pick disease type C: a case series Mol. Genet. Metab., 99 (2010), pp. 358–366
^ M. Masciullo, M. Santoro, A. Modoni, E. Ricci, J. Guitton, P. Tonali, G. Silvestri, Substrate reduction therapy with miglustat in chronic GM2 gangliosidosis type Sandhoff: results of a 3-year follow-up, J. Inherit. Metab. Dis. (2010) Sep 4.
^ Tomatsu, S., Mackenzie, W. G., Theroux, M. C., Mason, R. W., Thacker, M. M., Shaffer, T. H., ... & Orii, T. (2012). Current and emerging treatments and surgical interventions for Morquio A syndrome: a review. Research & Reports in Endocrine Disorders.
^ Rodríguez, A., Espejo, Á. J., Hernández, A., Velásquez, O. L., Lizaraso, L. M., Cordoba, H. A., ... & Barrera, L. A. (2010). Enzyme replacement therapy for Morquio A: an active recombinant N-acetylgalactosamine-6-sulfate sulfatase produced in Escherichia coli BL21. Journal of industrial microbiology & biotechnology, 37(11), 1193-1201.
^ http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm386008.htm

External links

Category:Autosomal recessive disorders Category:Rare diseases Category:Proteoglycan metabolism disorders Category:Skin conditions resulting from errors in metabolism

[Andrews-1] James, William D.; Berger, Timothy G. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. {{cite book}}: Invalid |display-authors=3 (help)

[pmid18456538-2] Prat C, Lemaire O, Bret J, Zabraniecki L, Fournié B (May 2008). "Morquio syndrome: Diagnosis in an adult". Joint Bone Spine. 75 (4): 495–8. doi:10.1016/j.jbspin.2007.07.021. PMID 18456538.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[3] Davison, J. E., Kearney, S., Horton, J., Foster, K., Peet, A. C., & Hendriksz, C. J. (2013). Intellectual and neurological functioning in Morquio syndrome (MPS IVa). Journal of inherited metabolic disease, 36(2), 323-328.

[4] Northover, H., Cowie, R. A., & Wraith, J. E. (1996). Mucopolysaccharidosis type IVA (Morquio syndrome): a clinical review. Journal of inherited metabolic disease, 19(3), 357-365.

[5] synd/2108 at Who Named It?

[6] Morquio, L. (1929). "Sur une forme de dystrophie osseuse familiale". Archives de médecine des infants. 32. Paris: 129–135. ISSN 0365-4311.

[7] Brailsford, J. F. (1929). "Chondro-osteo-dystrophy: Roentgenographic & clinical features of a child with dislocation of vertebrae". American Journal of Surgery. 7 (3). New York: 404–410. doi:10.1016/S0002-9610(29)90496-7.

[8] Y. Suzuki, A. Oshima, E. Namba β-Galactosidase deficiency (β-galactosidosis) GM1 gangliosidosis and Morquio B disease C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle (Eds.), The Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill, New York (2001), pp. 3775–3809

[9] Nelson, J. (1997). Incidence of the mucopolysaccharidoses in Northern Ireland. Human genetics, 101(3), 355-358.

[10] J. Nelson, J. Crowhurst, B. Carey, L. Greed Incidence of the mucopolysaccharidoses in Western Australia Am. J. Med. Genet. A, 123A (2003), pp. 310–313

[11] Borlot, F., Arantes, P. R., Cardoso, A. C. C., & Kim, C. A. (2014). Remote spinal cord injury in mucopolysaccharidosis type IVA after cervical decompression. Neurology, 82(15), 1382-1383.

[12] Montano, A. M., Tomatsu, S., Gottesman, G. S., Smith, M., & Orii, T. (2007). International Morquio A Registry: clinical manifestation and natural course of Morquio A disease. Journal of inherited metabolic disease, 30(2), 165-174.

[13] Blaw, M. E., & Langer, L. O. (1969). Spinal cord compression in Morquio-Brailsford's disease. The Journal of pediatrics, 74(4), 593-600.

[14] P. Giraldo, P. Alfonso, K. Atutxa, M.A. Fernández-Galán, A. Barez, R. Franco, D. Alonso, A. Martin, P. Latre, M. Pocovi Real-world clinical experience with long-term miglustat maintenance therapy in type 1 Gaucher disease: the ZAGAL project Haematologica, 94 (2009), pp. 1771–1775

[15] M. Pineda, M.S. Perez-Poyato, M. O'Callaghan, M.A. Vilaseca, M. Pocovi, R. Domingo, L.R. Portal, A.V. Pérez, T. Temudo, A. Gaspar, J.J. Peñas, S. Roldán, L.M. Fumero, O.B. de la Barca, M.T. Silva, J. Macías-Vidal, M.J. Coll Clinical experience with miglustat therapy in pediatric patients with Niemann–Pick disease type C: a case series Mol. Genet. Metab., 99 (2010), pp. 358–366

[16] M. Masciullo, M. Santoro, A. Modoni, E. Ricci, J. Guitton, P. Tonali, G. Silvestri, Substrate reduction therapy with miglustat in chronic GM2 gangliosidosis type Sandhoff: results of a 3-year follow-up, J. Inherit. Metab. Dis. (2010) Sep 4.

[17] Tomatsu, S., Mackenzie, W. G., Theroux, M. C., Mason, R. W., Thacker, M. M., Shaffer, T. H., ... & Orii, T. (2012). Current and emerging treatments and surgical interventions for Morquio A syndrome: a review. Research & Reports in Endocrine Disorders.

[18] Rodríguez, A., Espejo, Á. J., Hernández, A., Velásquez, O. L., Lizaraso, L. M., Cordoba, H. A., ... & Barrera, L. A. (2010). Enzyme replacement therapy for Morquio A: an active recombinant N-acetylgalactosamine-6-sulfate sulfatase produced in Escherichia coli BL21. Journal of industrial microbiology & biotechnology, 37(11), 1193-1201.

[19] ttp://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm386008.htm

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]