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Mucopolysaccharidosis type VII(MPS7)

MedGen UID:
43108
Concept ID:
C0085132
Disease or Syndrome
Synonyms: Beta-glucuronidase deficiency; MPS 7; MPS VII; MPS7; Mucopolysaccharidosis type 7; Sly syndrome
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Deficiency of beta-glucuronidase (124470009); Sly disease (43916004); Mucopolysaccharidosis type VII (43916004); Beta-glucuronidase deficiency (43916004); MPS VII - Mucopolysaccharidosis VII (43916004); Mucopolysaccharidosis, MPS-VII (43916004); Sly syndrome (43916004); beta-Glucuronidase deficiency (43916004); GUSB deficiency (43916004); GUS deficiency (43916004)
 
Gene (location): GUSB (7q11.21)
OMIM®: 253220
Orphanet: ORPHA584

Definition

Mucopolysaccharidosis type VII is an autosomal recessive lysosomal storage disease characterized by the inability to degrade glucuronic acid-containing glycosaminoglycans. The phenotype is highly variable, ranging from severe lethal hydrops fetalis to mild forms with survival into adulthood. Most patients with the intermediate phenotype show hepatomegaly, skeletal anomalies, coarse facies, and variable degrees of mental impairment (Shipley et al., 1993). MPS VII was the first autosomal mucopolysaccharidosis for which chromosomal assignment was achieved. [from OMIM]

Additional description

From GHR
Mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, is a progressive condition that affects most tissues and organs. The severity of MPS VII varies widely among affected individuals.The most severe cases of MPS VII are characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Most babies with hydrops fetalis are stillborn or die soon after birth. Other people with MPS VII typically begin to show signs and symptoms of the condition during early childhood. The features of MPS VII include a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), distinctive-looking facial features that are described as "coarse," and a large tongue (macroglossia). Affected individuals also frequently develop an enlarged liver and spleen (hepatosplenomegaly), heart valve abnormalities, and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). The airway may become narrow in some people with MPS VII, leading to frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). The clear covering of the eye (cornea) becomes cloudy, which can cause significant vision loss. People with MPS VII may also have recurrent ear infections and hearing loss. Affected individuals may have developmental delay and progressive intellectual disability, although intelligence is unaffected in some people with this condition.MPS VII causes various skeletal abnormalities that become more pronounced with age, including short stature and joint deformities (contractures) that affect mobility. Individuals with this condition may also have dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Carpal tunnel syndrome develops in many children with MPS VII and is characterized by numbness, tingling, and weakness in the hands and fingers. People with MPS VII may develop a narrowing of the spinal canal (spinal stenosis) in the neck, which can compress and damage the spinal cord.The life expectancy of individuals with MPS VII depends on the severity of symptoms. Some affected individuals do not survive infancy, while others may live into adolescence or adulthood. Heart disease and airway obstruction are major causes of death in people with MPS VII.  https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-vii

Clinical features

Corneal opacity
MedGen UID:
40485
Concept ID:
C0010038
Finding
A reduction of corneal clarity.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormal enlargement of the liver.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
An abdominal hernia with an external bulge in the GROIN region. It can be classified by the location of herniation. Indirect inguinal hernias occur through the internal inguinal ring. Direct inguinal hernias occur through defects in the ABDOMINAL WALL (transversalis fascia) in Hesselbach's triangle. The former type is commonly seen in children and young adults; the latter in adults.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Disease or Syndrome
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
Hirsutism
MedGen UID:
42461
Concept ID:
C0019572
Finding
A condition observed in WOMEN and CHILDREN when there is excess coarse body hair of an adult male distribution pattern, such as facial and chest areas. It is the result of elevated ANDROGENS from the OVARIES, the ADRENAL GLANDS, or exogenous sources. The concept does not include HYPERTRICHOSIS, which is an androgen-independent excessive hair growth.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Autosomal recessive nonsyndromic hydrocephalus is characterized by onset in utero of enlarged ventricles due to a disturbance of cerebrospinal fluid accumulation. Affected individuals may have neurologic impairment (summary by Drielsma et al., 2012). Hydrocephalus can also be caused by Arnold-Chiari malformation, atresia of foramen of Magendie, stenosis of aqueduct of Sylvius (307000), toxoplasmosis, hydranencephaly, etc. Furthermore, it develops in infancy or childhood in achondroplasia (100800) and in Hurler disease (607014). Genetic Heterogeneity of Congenital Hydrocephalus See also autosomal recessive HYC2 (615219), caused by mutation in the MPDZ gene (603785) on chromosome 9p. An X-linked form (307000) is caused by mutation in the L1CAM gene on (308840) on chromosome Xq28.
Hydrops fetalis
MedGen UID:
6947
Concept ID:
C0020305
Disease or Syndrome
A condition characterized by fluid accumulation in two or more anatomic compartments in the fetus.(NICHD)
Neurodegeneration
MedGen UID:
17999
Concept ID:
C0027746
Cell or Molecular Dysfunction
Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal enlargement of the spleen.
Dysostosis multiplex
MedGen UID:
39698
Concept ID:
C0086795
Disease or Syndrome
Mucopolysaccharidosis type I (MPS I) is a progressive multisystem disorder with features ranging over a continuum of severity. While affected individuals have traditionally been classified as having one of three MPS I syndromes (Hurler syndrome, Hurler-Scheie syndrome, or Scheie syndrome), no easily measurable biochemical differences have been identified and the clinical findings overlap; thus, affected individuals are best described as having either severe or attenuated MPS I, a distinction that influences therapeutic options. Severe MPS I. Infants appear normal at birth. Typical early manifestations are nonspecific (e.g., umbilical or inguinal hernia, frequent upper respiratory-tract infections before age 1 year). Coarsening of the facial features may not become apparent until after age one year. Gibbus deformity of the lower spine is common and often noted within the first year. Progressive skeletal dysplasia (dysostosis multiplex) involving all bones is universal. By age three years, linear growth decreases. Intellectual disability is progressive and profound. Hearing loss is common. Death, typically caused by cardiorespiratory failure, usually occurs within the first ten years of life. Attenuated MPS I. The severity and rate of disease progression range from serious life-threatening complications leading to death in the second to third decades to a normal life span complicated by significant disability from progressive joint manifestations and cardiorespiratory disease. While some individuals have no neurologic involvement and psychomotor development may be normal in early childhood, learning disabilities can be present. Clinical onset is usually between ages three and ten years. Hearing loss and cardiac valvular disease are common.
Pectus carinatum
MedGen UID:
57643
Concept ID:
C0158731
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
Abnormality of the heart valves
MedGen UID:
892837
Concept ID:
C0241654
Finding
An abnormality of a cardiac valve.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Narrow greater sacrosciatic notches
MedGen UID:
154353
Concept ID:
C0566888
Finding
A narrowing of the sacrosciatic notch, i.e., the deep indentation in the posterior border of the hip bone at the point of union of the ilium and ischium.
Acetabular dysplasia
MedGen UID:
233069
Concept ID:
C1328407
Anatomical Abnormality
The presence of developmental dysplasia of the acetabular part of hip bone.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Hypoplasia of the odontoid process
MedGen UID:
339524
Concept ID:
C1846439
Finding
The odontoid process, or dens, is a bony projection from the axis (C2) upward into the ring of the atlas (C1) at the top of the spine. During embryogenesis, the body of the odontoid derives from the centrum of the atlas and separates from the atlas, fusing with the superior portion of the axis. If the odontoid is hypoplastic or absent, the attachments for the apical and alar ligaments are missing, allowing for excessive rotation of the atlas, craniocervical instability, and possibly cord compression (summary by Stevens et al., 2009).
J-shaped sella turcica
MedGen UID:
381480
Concept ID:
C1854718
Finding
A deformity of the sella turcica whereby the sella extends further anterior than normal such that the anterior clinoid process appears to overhang it, giving the appearance of the letter J on imaging of the skull.
Proximal tapering of metacarpals
MedGen UID:
343199
Concept ID:
C1854749
Finding
Some or all of the metacarpal bones (i.e., metacarpal II to V) have a pointed proximal appearance.
Dermatan sulfate excretion in urine
MedGen UID:
343207
Concept ID:
C1854774
Finding
An increased concentration of dermatan sulfate in the urine.
Thoracolumbar kyphosis
MedGen UID:
383679
Concept ID:
C1855418
Anatomical Abnormality
Hyperconvexity of the thoracolumbar spine producing a rounded or humped appearance.
Postnatal growth retardation
MedGen UID:
395343
Concept ID:
C1859778
Finding
Slow or limited growth after birth.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Anterior beaking of lumbar vertebrae
MedGen UID:
867183
Concept ID:
C4021541
Anatomical Abnormality
Anterior tongue-like protrusions of the vertebral bodies of the lumbar spine.
Urinary glycosaminoglycan excretion
MedGen UID:
871129
Concept ID:
C4025598
Finding
Excretion of glycosaminoglycan in the urine. Glycosaminoglycans are long unbranched polysaccharides consisting of a repeating disaccharide unit.
Metatarsus adductus
MedGen UID:
898667
Concept ID:
C4082169
Anatomical Abnormality
The metatarsals are deviated medially (tibially), that is, the bones in the front half of the foot bend or turn in toward the body.
Increased head circumference
MedGen UID:
909477
Concept ID:
C4083076
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
MedGen UID:
505660
Concept ID:
CN004085

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMucopolysaccharidosis type VII
Follow this link to review classifications for Mucopolysaccharidosis type VII in Orphanet.

Recent clinical studies

Etiology

Montaño AM, Lock-Hock N, Steiner RD, Graham BH, Szlago M, Greenstein R, Pineda M, Gonzalez-Meneses A, Çoker M, Bartholomew D, Sands MS, Wang R, Giugliani R, Macaya A, Pastores G, Ketko AK, Ezgü F, Tanaka A, Arash L, Beck M, Falk RE, Bhattacharya K, Franco J, White KK, Mitchell GA, Cimbalistiene L, Holtz M, Sly WS
J Med Genet 2016 Jun;53(6):403-18. Epub 2016 Feb 23 doi: 10.1136/jmedgenet-2015-103322. PMID: 26908836Free PMC Article
Khan FI, Shahbaaz M, Bisetty K, Waheed A, Sly WS, Ahmad F, Hassan MI
Gene 2016 Jan 15;576(1 Pt 1):36-44. Epub 2015 Sep 28 doi: 10.1016/j.gene.2015.09.062. PMID: 26415878
Saxonhouse MA, Behnke M, Williams JL, Richards D, Weiss MD
J Perinatol 2003 Jan;23(1):73-5. doi: 10.1038/sj.jp.7210844. PMID: 12556933
den Hollander NS, Kleijer WJ, Schoonderwaldt EM, Los FJ, Wladimiroff JW, Niermeijer MF
Ultrasound Obstet Gynecol 2000 Jul;16(1):87-90. doi: 10.1046/j.1469-0705.2000.00148.x. PMID: 11084974
Stein CS, Ghodsi A, Derksen T, Davidson BL
J Virol 1999 Apr;73(4):3424-9. PMID: 10074197Free PMC Article

Diagnosis

Montaño AM, Lock-Hock N, Steiner RD, Graham BH, Szlago M, Greenstein R, Pineda M, Gonzalez-Meneses A, Çoker M, Bartholomew D, Sands MS, Wang R, Giugliani R, Macaya A, Pastores G, Ketko AK, Ezgü F, Tanaka A, Arash L, Beck M, Falk RE, Bhattacharya K, Franco J, White KK, Mitchell GA, Cimbalistiene L, Holtz M, Sly WS
J Med Genet 2016 Jun;53(6):403-18. Epub 2016 Feb 23 doi: 10.1136/jmedgenet-2015-103322. PMID: 26908836Free PMC Article
Gniadek TJ, Singer N, Barker NJ, Spevak PJ, Crain BJ, Valle D, Halushka MK
Cardiovasc Pathol 2015 Sep-Oct;24(5):322-6. Epub 2015 Jun 19 doi: 10.1016/j.carpath.2015.06.001. PMID: 26141114
Nampoothiri S, Kappanayil M, Hiran KR, Sunitha V
Indian Pediatr 2008 Oct;45(10):859-61. PMID: 18948660
Montaño AM, Oikawa H, Tomatsu S, Nishioka T, Vogler C, Gutierrez MA, Oguma T, Tan Y, Grubb JH, Dung VC, Ohashi A, Miyamoto K, Orii T, Yoneda Y, Sly WS
Mol Genet Metab 2008 Jun;94(2):178-89. Epub 2008 Mar 21 doi: 10.1016/j.ymgme.2008.01.007. PMID: 18359257
Dickerman RD, Colle KO, Bruno CA Jr, Schneider SJ
Spine (Phila Pa 1976) 2004 Mar 1;29(5):E92-4. PMID: 15129089

Therapy

Sands MS
Pediatr Endocrinol Rev 2014 Sep;12 Suppl 1:159-65. PMID: 25345098
Montaño AM, Oikawa H, Tomatsu S, Nishioka T, Vogler C, Gutierrez MA, Oguma T, Tan Y, Grubb JH, Dung VC, Ohashi A, Miyamoto K, Orii T, Yoneda Y, Sly WS
Mol Genet Metab 2008 Jun;94(2):178-89. Epub 2008 Mar 21 doi: 10.1016/j.ymgme.2008.01.007. PMID: 18359257
Nakama H, Ohsugi K, Otsuki T, Date I, Kosuga M, Okuyama T, Sakuragawa N
Tohoku J Exp Med 2006 May;209(1):23-32. PMID: 16636519
Hofling AA, Sands MS, Lublin DM, Bauer G, Devine S
J Clin Apher 2004;19(3):151-3. doi: 10.1002/jca.20018. PMID: 15493049
LeBowitz JH, Grubb JH, Maga JA, Schmiel DH, Vogler C, Sly WS
Proc Natl Acad Sci U S A 2004 Mar 2;101(9):3083-8. Epub 2004 Feb 19 doi: 10.1073/pnas.0308728100. PMID: 14976248Free PMC Article

Prognosis

Montaño AM, Lock-Hock N, Steiner RD, Graham BH, Szlago M, Greenstein R, Pineda M, Gonzalez-Meneses A, Çoker M, Bartholomew D, Sands MS, Wang R, Giugliani R, Macaya A, Pastores G, Ketko AK, Ezgü F, Tanaka A, Arash L, Beck M, Falk RE, Bhattacharya K, Franco J, White KK, Mitchell GA, Cimbalistiene L, Holtz M, Sly WS
J Med Genet 2016 Jun;53(6):403-18. Epub 2016 Feb 23 doi: 10.1136/jmedgenet-2015-103322. PMID: 26908836Free PMC Article
Fox JE, Volpe L, Bullaro J, Kakkis ED, Sly WS
Mol Genet Metab 2015 Feb;114(2):203-8. Epub 2014 Nov 7 doi: 10.1016/j.ymgme.2014.10.017. PMID: 25468648Free PMC Article
Saxonhouse MA, Behnke M, Williams JL, Richards D, Weiss MD
J Perinatol 2003 Jan;23(1):73-5. doi: 10.1038/sj.jp.7210844. PMID: 12556933
Vogler C, Sands MS, Galvin N, Levy B, Thorpe C, Barker J, Sly WS
J Inherit Metab Dis 1998 Aug;21(5):575-86. PMID: 9728337
Molyneux AJ, Blair E, Coleman N, Daish P
J Clin Pathol 1997 Mar;50(3):252-4. PMID: 9155679Free PMC Article

Clinical prediction guides

Montaño AM, Lock-Hock N, Steiner RD, Graham BH, Szlago M, Greenstein R, Pineda M, Gonzalez-Meneses A, Çoker M, Bartholomew D, Sands MS, Wang R, Giugliani R, Macaya A, Pastores G, Ketko AK, Ezgü F, Tanaka A, Arash L, Beck M, Falk RE, Bhattacharya K, Franco J, White KK, Mitchell GA, Cimbalistiene L, Holtz M, Sly WS
J Med Genet 2016 Jun;53(6):403-18. Epub 2016 Feb 23 doi: 10.1136/jmedgenet-2015-103322. PMID: 26908836Free PMC Article
Kanaji A, Kosuga M, Li XK, Fukuhara Y, Tanabe A, Kamata Y, Azuma N, Yamada M, Sakamaki T, Toyama Y, Okuyama T
Mol Ther 2003 Nov;8(5):718-25. PMID: 14599804
Meng XL, Shen JS, Ohashi T, Maeda H, Kim SU, Eto Y
J Neurosci Res 2003 Oct 15;74(2):266-77. doi: 10.1002/jnr.10764. PMID: 14515356
Kamata Y, Okuyama T, Kosuga M, O'hira A, Kanaji A, Sasaki K, Yamada M, Azuma N
Mol Ther 2001 Oct;4(4):307-12. doi: 10.1006/mthe.2001.0461. PMID: 11592832
Kosuga M, Sasaki K, Tanabe A, Li XK, Okawa H, Ogino I, Okuda O, Arai H, Sakuragawa N, Kamata Y, Azuma N, Suzuki S, Yamada M, Okuyama T
Mol Ther 2001 Feb;3(2):139-48. doi: 10.1006/mthe.2000.0234. PMID: 11237670

Recent systematic reviews

Gimovsky AC, Luzi P, Berghella V
Am J Obstet Gynecol 2015 Mar;212(3):281-90. Epub 2014 Oct 8 doi: 10.1016/j.ajog.2014.10.007. PMID: 25305402

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