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Mucopolysaccharidosis, MPS-IV-A(MPS4A)

MedGen UID:
43375
Concept ID:
C0086651
Disease or Syndrome
Synonyms: Galactosamine-6-sulfatase deficiency; Morquio A disease; Morquio syndrome A; Morquio syndrome A, mild; MPS 4A; MPS IVA; MPS4A; Mucopolysaccharidosis type IV A; Mucopolysaccharidosis Type IVA
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
SNOMED CT: Galactose-6-sulfatase deficiency (7259005); Galactosamine-6-sulfatase deficiency (7259005); MPS IV-A-Mucopolysaccharidosis IV-A (7259005); Mucopolysaccharidosis IV-A (7259005); Morquio syndrome A (7259005); Mucopolysaccharidosis, MPS-IV-A (7259005); Morquio's syndrome, classic form (7259005); N-acetylgalactosamine-6-sulfatase deficiency (7259005); Morquio A syndrome (7259005); Deficiency of chondroitinase (130197005); Deficiency of galactose-6-sulfate sulfatase (130197005); Deficiency of chondroitinsulfatase (130197005); Deficiency of N-acetylgalactosamine-6-sulfatase (130197005)
 
Gene: GALNS
Cytogenetic location: 16q24.3
OMIM: 253000

Definition

Mucopolysaccharidosis type IVA is an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of keratan sulfate and chondroitin-6-sulfate. Key clinical features include short stature, skeletal dysplasia, dental anomalies, and corneal clouding. Intelligence is normal and there is no direct central nervous system involvement, although the skeletal changes may result in neurologic complications. There is variable severity, but patients with the severe phenotype usually do not survive past the second or third decade of life (Montano et al., 2008). McKusick (1972) noted that between 1929 and 1959, a miscellany of skeletal disorders was included in the Morquio category, including various types of spondyloepiphyseal dysplasia (see, e.g., 183900) and multiple epiphyseal dysplasia (see, e.g., 132400). Nelson et al. (1988) proposed the division of MPS IVA into 3 subgroups: severe classic, intermediate, and mild, reflecting clinical variability observed in 12 enzymatically proven cases. Those who were only mildly affected showed a relatively high residual enzyme activity. [from OMIM]

Additional description

From GHR
Mucopolysaccharidosis type IV (MPS IV), also known as Morquio syndrome, is a progressive condition that mainly affects the skeleton. The rate at which symptoms worsen varies among affected individuals. The first signs and symptoms of MPS IV 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. In people with MPS IV, the clear covering of the eye (cornea) typically becomes cloudy, which can cause vision loss. Some affected individuals have recurrent ear infections and hearing loss. The airway may become narrow in some people with MPS IV, leading to frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). Other common features of this condition include mildly "coarse" facial features, thin tooth enamel, multiple cavities, heart valve abnormalities, a mildly enlarged liver (hepatomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). Unlike some other types of mucopolysaccharidosis, MPS IV does not affect intelligence. The life expectancy of individuals with MPS IV depends on the severity of symptoms. Severely affected individuals may survive only until late childhood or adolescence. Those with milder forms of the disorder usually live into adulthood, although their life expectancy may be reduced. Spinal cord compression and airway obstruction are major causes of death in people with MPS IV.  http://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iv

Clinical features

Keratan sulfate excretion in urine
MedGen UID:
489589
Concept ID:
CN167795
Finding
An `increased concentration` (PATO:0001162) of `keratan sulfate` (CHEBI:60924) in the `urine` (FMA:12274).
Chondroitin sulfate excretion in urine
MedGen UID:
489590
Concept ID:
CN167796
Finding
An `increased concentration` (PATO:0001162) of `chondroitin sulfate (CHEBI:37397) in the `urine` (FMA:12274).
Wide mouth
MedGen UID:
504368
Concept ID:
CN000150
Finding
Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).
Mandibular prognathia
MedGen UID:
427817
Concept ID:
CN000285
Finding
Abnormal prominence of the `chin` (FMA:46495) related to `increased length` (PATO:0000573) of the `mandible` (FMA:52748).
Recurrent upper respiratory tract infections
MedGen UID:
500940
Concept ID:
CN002522
Finding
An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
Hearing impairment
MedGen UID:
446352
Concept ID:
CN000341
Finding
A `decreased magnitude` (PATO:0002018) of the `sensory perception of sound` (GO:0007605).
Coxa valga
MedGen UID:
116080
Concept ID:
C0239137
Finding
Hip deformity in which the angle between the femoral neck and its shaft is increased. It may be congenital, acquired, or developmental.
Metaphyseal widening
MedGen UID:
344455
Concept ID:
C1855248
Finding
A radiologic finding characterized by an increased width of the metaphyseal regions. It is seen in rickets.
Mandibular prognathia
MedGen UID:
427817
Concept ID:
CN000285
Finding
Abnormal prominence of the `chin` (FMA:46495) related to `increased length` (PATO:0000573) of the `mandible` (FMA:52748).
Joint laxity
MedGen UID:
504825
Concept ID:
CN001270
Finding
Lack of stability of a joint.
Scoliosis
MedGen UID:
427922
Concept ID:
CN002409
Finding
The presence of an abnormal lateral curvature of the spine.
Genu valgum
MedGen UID:
505373
Concept ID:
CN002582
Finding
The legs angle inward, such that the knees are close together and the ankles far apart.
Hyperlordosis
MedGen UID:
505513
Concept ID:
CN002983
Finding
Abnormally increased cuvature (anterior concavity) of the lumbar or cervical spine.
Hypoplasia of the odontoid process
MedGen UID:
500949
Concept ID:
CN002987
Finding
Developmental hypoplasia of the `dens of the axis` (FMA:24043).
Disproportionate short-trunk short stature
MedGen UID:
500958
Concept ID:
CN003177
Finding
A type of `disproportionate short stature` (HP:0003498) characterized by a short trunk but a average-sized limbs.
Inguinal hernia
MedGen UID:
504305
Concept ID:
CN000024
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Hepatomegaly
MedGen UID:
505165
Concept ID:
CN002031
Finding
Abnormally `increased size` (PATO:0000586) of the `liver` (FMA:7197).
Disproportionate short-trunk short stature
MedGen UID:
500958
Concept ID:
CN003177
Finding
A type of `disproportionate short stature` (HP:0003498) characterized by a short trunk but a average-sized limbs.
Abnormality of the heart valves
MedGen UID:
446421
Concept ID:
CN001506
Finding
An abnormality of a `Cardiac valve` (FMA:7110).
Keratan sulfate excretion in urine
MedGen UID:
489589
Concept ID:
CN167795
Finding
An `increased concentration` (PATO:0001162) of `keratan sulfate` (CHEBI:60924) in the `urine` (FMA:12274).
Chondroitin sulfate excretion in urine
MedGen UID:
489590
Concept ID:
CN167796
Finding
An `increased concentration` (PATO:0001162) of `chondroitin sulfate (CHEBI:37397) in the `urine` (FMA:12274).
Recurrent upper respiratory tract infections
MedGen UID:
500940
Concept ID:
CN002522
Finding
An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
Recurrent upper respiratory tract infections
MedGen UID:
500940
Concept ID:
CN002522
Finding
An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
Inguinal hernia
MedGen UID:
504305
Concept ID:
CN000024
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.

Recent clinical studies

Etiology

Cavaleiro RM, Pinheiro Md, Pinheiro LR, Tuji FM, Feio Pdo S, de Souza IC, Feio RH, de Almeida SC, Schwartz IV, Giugliani R, Pinheiro JJ, Santana-da-Silva LC
Oral Surg Oral Med Oral Pathol Oral Radiol 2013 Aug;116(2):e141-8. doi: 10.1016/j.oooo.2013.04.021. PMID: 23849382
Park HD, Ko AR, Ki CS, Lee SY, Kim JW, Cho SY, Kim SH, Park SW, Sohn YB, Jin DK
Am J Med Genet A 2013 Mar;161A(3):509-17. Epub 2013 Feb 8 doi: 10.1002/ajmg.a.35298. [Epub ahead of print] PMID: 23401410
Wood TC, Harvey K, Beck M, Burin MG, Chien YH, Church HJ, D'Almeida V, van Diggelen OP, Fietz M, Giugliani R, Harmatz P, Hawley SM, Hwu WL, Ketteridge D, Lukacs Z, Miller N, Pasquali M, Schenone A, Thompson JN, Tylee K, Yu C, Hendriksz CJ
J Inherit Metab Dis 2013 Mar;36(2):293-307. Epub 2013 Feb 1 doi: 10.1007/s10545-013-9587-1. [Epub ahead of print] PMID: 23371450Free PMC Article
Dhawale AA, Thacker MM, Belthur MV, Rogers K, Bober MB, Mackenzie WG
J Pediatr Orthop 2012 Jul-Aug;32(5):534-40. doi: 10.1097/BPO.0b013e318259fe57. PMID: 22706472
Lin HY, Chen MR, Chuang CK, Chen CP, Lin DS, Chien YH, Ke YY, Tsai FJ, Pan HP, Lin SJ, Hwu WL, Niu DM, Lee NC, Lin SP
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S421-7. Epub 2010 Oct 6 doi: 10.1007/s10545-010-9212-5. [Epub ahead of print] PMID: 20924685

Diagnosis

Cavaleiro RM, Pinheiro Md, Pinheiro LR, Tuji FM, Feio Pdo S, de Souza IC, Feio RH, de Almeida SC, Schwartz IV, Giugliani R, Pinheiro JJ, Santana-da-Silva LC
Oral Surg Oral Med Oral Pathol Oral Radiol 2013 Aug;116(2):e141-8. doi: 10.1016/j.oooo.2013.04.021. PMID: 23849382
Hendriksz CJ, Harmatz P, Beck M, Jones S, Wood T, Lachman R, Gravance CG, Orii T, Tomatsu S
Mol Genet Metab 2013 Sep-Oct;110(1-2):54-64. Epub 2013 Apr 10 doi: 10.1016/j.ymgme.2013.04.002. [Epub ahead of print] PMID: 23665161Free PMC Article
Solanki GA, Martin KW, Theroux MC, Lampe C, White KK, Shediac R, Lampe CG, Beck M, Mackenzie WG, Hendriksz CJ, Harmatz PR
J Inherit Metab Dis 2013 Mar;36(2):339-55. Epub 2013 Feb 6 doi: 10.1007/s10545-013-9586-2. [Epub ahead of print] PMID: 23385297Free PMC Article
Wood TC, Harvey K, Beck M, Burin MG, Chien YH, Church HJ, D'Almeida V, van Diggelen OP, Fietz M, Giugliani R, Harmatz P, Hawley SM, Hwu WL, Ketteridge D, Lukacs Z, Miller N, Pasquali M, Schenone A, Thompson JN, Tylee K, Yu C, Hendriksz CJ
J Inherit Metab Dis 2013 Mar;36(2):293-307. Epub 2013 Feb 1 doi: 10.1007/s10545-013-9587-1. [Epub ahead of print] PMID: 23371450Free PMC Article
Kubaski F, Brusius-Facchin AC, Palhares HM, Balarin MA, Viapiana-Camelier M, Guidobono R, Burin MG, Giugliani R, Leistner-Segal S
Gene 2013 Mar 15;517(1):112-5. Epub 2013 Jan 11 doi: 10.1016/j.gene.2012.12.100. [Epub ahead of print] PMID: 23313879

Therapy

Borlot F, Arantes PR, Capel Cardoso AC, Kim CA
Neurology 2014 Apr 15;82(15):1382-3. doi: 10.1212/WNL.0000000000000341. PMID: 24733857
Furujo M, Kubo T, Kosuga M, Okuyama T
Mol Genet Metab 2011 Dec;104(4):597-602. Epub 2011 Aug 28 doi: 10.1016/j.ymgme.2011.08.029. [Epub ahead of print] PMID: 21930407
Khaliq T, Sadilek M, Scott CR, Turecek F, Gelb MH
Clin Chem 2011 Jan;57(1):128-31. Epub 2010 Oct 28 doi: 10.1373/clinchem.2010.149880. [Epub ahead of print] PMID: 21030685Free PMC Article
Lin HY, Chen MR, Chuang CK, Chen CP, Lin DS, Chien YH, Ke YY, Tsai FJ, Pan HP, Lin SJ, Hwu WL, Niu DM, Lee NC, Lin SP
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S421-7. Epub 2010 Oct 6 doi: 10.1007/s10545-010-9212-5. [Epub ahead of print] PMID: 20924685
Dvorak-Ewell M, Wendt D, Hague C, Christianson T, Koppaka V, Crippen D, Kakkis E, Vellard M
PLoS One 2010 Aug 16;5(8):e12194. doi: 10.1371/journal.pone.0012194. PMID: 20808938Free PMC Article

Prognosis

He D, Huang Y, Ou Z, Sheng H, Li S, Zhao X, Li R, Zheng J, Liu L
Gene 2013 Dec 10;532(1):46-52. Epub 2013 Sep 11 doi: 10.1016/j.gene.2013.08.097. [Epub ahead of print] PMID: 24035930
Dũng VC, Tomatsu S, Montaño AM, Gottesman G, Bober MB, Mackenzie W, Maeda M, Mitchell GA, Suzuki Y, Orii T
Mol Genet Metab 2013 Sep-Oct;110(1-2):129-38. Epub 2013 Jun 26 doi: 10.1016/j.ymgme.2013.06.008. [Epub ahead of print] PMID: 23876334Free PMC Article
Cavaleiro RM, Pinheiro Md, Pinheiro LR, Tuji FM, Feio Pdo S, de Souza IC, Feio RH, de Almeida SC, Schwartz IV, Giugliani R, Pinheiro JJ, Santana-da-Silva LC
Oral Surg Oral Med Oral Pathol Oral Radiol 2013 Aug;116(2):e141-8. doi: 10.1016/j.oooo.2013.04.021. PMID: 23849382
Kubaski F, Brusius-Facchin AC, Palhares HM, Balarin MA, Viapiana-Camelier M, Guidobono R, Burin MG, Giugliani R, Leistner-Segal S
Gene 2013 Mar 15;517(1):112-5. Epub 2013 Jan 11 doi: 10.1016/j.gene.2012.12.100. [Epub ahead of print] PMID: 23313879
Dhawale AA, Thacker MM, Belthur MV, Rogers K, Bober MB, Mackenzie WG
J Pediatr Orthop 2012 Jul-Aug;32(5):534-40. doi: 10.1097/BPO.0b013e318259fe57. PMID: 22706472

Clinical prediction guides

Dũng VC, Tomatsu S, Montaño AM, Gottesman G, Bober MB, Mackenzie W, Maeda M, Mitchell GA, Suzuki Y, Orii T
Mol Genet Metab 2013 Sep-Oct;110(1-2):129-38. Epub 2013 Jun 26 doi: 10.1016/j.ymgme.2013.06.008. [Epub ahead of print] PMID: 23876334Free PMC Article
Cavaleiro RM, Pinheiro Md, Pinheiro LR, Tuji FM, Feio Pdo S, de Souza IC, Feio RH, de Almeida SC, Schwartz IV, Giugliani R, Pinheiro JJ, Santana-da-Silva LC
Oral Surg Oral Med Oral Pathol Oral Radiol 2013 Aug;116(2):e141-8. doi: 10.1016/j.oooo.2013.04.021. PMID: 23849382
Hendriksz CJ, Harmatz P, Beck M, Jones S, Wood T, Lachman R, Gravance CG, Orii T, Tomatsu S
Mol Genet Metab 2013 Sep-Oct;110(1-2):54-64. Epub 2013 Apr 10 doi: 10.1016/j.ymgme.2013.04.002. [Epub ahead of print] PMID: 23665161Free PMC Article
Harmatz P, Mengel KE, Giugliani R, Valayannopoulos V, Lin SP, Parini R, Guffon N, Burton BK, Hendriksz CJ, Mitchell J, Martins A, Jones S, Guelbert N, Vellodi A, Hollak C, Slasor P, Decker C
Mol Genet Metab 2013 May;109(1):54-61. Epub 2013 Feb 9 doi: 10.1016/j.ymgme.2013.01.021. [Epub ahead of print] PMID: 23452954
Kubaski F, Brusius-Facchin AC, Palhares HM, Balarin MA, Viapiana-Camelier M, Guidobono R, Burin MG, Giugliani R, Leistner-Segal S
Gene 2013 Mar 15;517(1):112-5. Epub 2013 Jan 11 doi: 10.1016/j.gene.2012.12.100. [Epub ahead of print] PMID: 23313879

Recent systematic reviews

Frawley G, Fuenzalida D, Donath S, Yaplito-Lee J, Peters H
Paediatr Anaesth 2012 Aug;22(8):737-44. Epub 2012 Mar 2 doi: 10.1111/j.1460-9592.2012.03825.x. [Epub ahead of print] PMID: 22381044
Caciotti A, Garman SC, Rivera-Colón Y, Procopio E, Catarzi S, Ferri L, Guido C, Martelli P, Parini R, Antuzzi D, Battini R, Sibilio M, Simonati A, Fontana E, Salviati A, Akinci G, Cereda C, Dionisi-Vici C, Deodato F, d'Amico A, d'Azzo A, Bertini E, Filocamo M, Scarpa M, di Rocco M, Tifft CJ, Ciani F, Gasperini S, Pasquini E, Guerrini R, Donati MA, Morrone A
Biochim Biophys Acta 2011 Jul;1812(7):782-90. Epub 2011 Apr 7 doi: 10.1016/j.bbadis.2011.03.018. [Epub ahead of print] PMID: 21497194Free PMC Article

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