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Mucopolysaccharidosis type 7(MPS7)

MedGen UID:
43108
Concept ID:
C0085132
Disease or Syndrome
Synonyms: Beta-glucuronidase deficiency; MPS 7; MPS VII; MPS7; Mucopolysaccharidosis type VII; Sly syndrome
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)
 
Monarch Initiative: MONDO:0009662
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 MedlinePlus Genetics
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.\n\nThe 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.\n\nMPS 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.\n\nThe 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://medlineplus.gov/genetics/condition/mucopolysaccharidosis-type-vii

Clinical features

From HPO
Dermatan sulfate excretion in urine
MedGen UID:
343207
Concept ID:
C1854774
Finding
An increased concentration of dermatan sulfate in the urine.
Heparan sulfate excretion in urine
MedGen UID:
340721
Concept ID:
C1854827
Finding
An increased concentration of heparan sulfates in the urine.
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.
Talipes equinovarus
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Acetabular dysplasia
MedGen UID:
233069
Concept ID:
C1328407
Anatomical Abnormality
The presence of developmental dysplasia of the acetabular part of hip bone.
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.
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.
Abnormal heart valve morphology
MedGen UID:
892837
Concept ID:
C0241654
Finding
Any structural abnormality of a cardiac valve.
Cardiomyopathy
MedGen UID:
209232
Concept ID:
C0878544
Disease or Syndrome
A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.
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 \
Postnatal growth retardation
MedGen UID:
395343
Concept ID:
C1859778
Finding
Slow or limited growth after birth.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Neurodegeneration
MedGen UID:
17999
Concept ID:
C0027746
Cell or Molecular Dysfunction
Progressive loss of neural cells and tissue.
Poor speech
MedGen UID:
341172
Concept ID:
C1848207
Finding
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.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Hurler syndrome
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. Affected individuals are best described as having either a phenotype consistent with either severe (Hurler syndrome) 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, as is progressive arthropathy involving most joints. By age three years, linear growth decreases. Intellectual disability is progressive and profound but may not be readily apparent in the first year of life. Progressive cardiorespiratory involvement, hearing loss, and corneal clouding are common. Without treatment, death (typically from cardiorespiratory failure) usually occurs within the first ten years of life. Attenuated MPS I. Clinical onset is usually between ages three and ten years. The severity and rate of disease progression range from serious life-threatening complications leading to death in the second to third decade, 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 and psychiatric manifestations can be present later in life. Hearing loss, cardiac valvular disease, respiratory involvement, and corneal clouding 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.
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 neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Narrow greater sciatic notch
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.
Genu valgum
MedGen UID:
154364
Concept ID:
C0576093
Anatomical Abnormality
The legs angle inward, such that the knees are close together and the ankles far apart.
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
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.
Thoracolumbar kyphosis
MedGen UID:
383679
Concept ID:
C1855418
Anatomical Abnormality
Hyperconvexity of the thoracolumbar spine producing a rounded or humped appearance.
Macrocephalus
MedGen UID:
745757
Concept ID:
C2243051
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.
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.
Anterior beaking of lower thoracic vertebrae
MedGen UID:
870846
Concept ID:
C4025306
Anatomical Abnormality
Anterior tongue-like protrusions of the lower thoracic vertebral bodies.
Decreased pulmonary function
MedGen UID:
68612
Concept ID:
C0235063
Pathologic Function
A decrease in ventilation secondary to impaired signals from the central nervous system.
Recurrent upper respiratory tract infections
MedGen UID:
154380
Concept ID:
C0581381
Disease or Syndrome
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).
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Abnormality of the dentition
MedGen UID:
78084
Concept ID:
C0262444
Finding
Any abnormality of the teeth.
Gingival overgrowth
MedGen UID:
87712
Concept ID:
C0376480
Finding
Hyperplasia of the gingiva (that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown.
Widely spaced teeth
MedGen UID:
337093
Concept ID:
C1844813
Finding
Increased spaces (diastemata) between most of the teeth in the same dental arch.
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.
Thick eyebrow
MedGen UID:
377914
Concept ID:
C1853487
Finding
Increased density/number and/or increased diameter of eyebrow hairs.
Hirsutism
MedGen UID:
42461
Concept ID:
C0019572
Disease or Syndrome
Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair).
Hydrops fetalis
MedGen UID:
6947
Concept ID:
C0020305
Disease or Syndrome
The abnormal accumulation of fluid in two or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema.
Corneal opacity
MedGen UID:
40485
Concept ID:
C0010038
Finding
A reduction of corneal clarity.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMucopolysaccharidosis type 7
Follow this link to review classifications for Mucopolysaccharidosis type 7 in Orphanet.

Recent clinical studies

Etiology

Breyer SR, Vettorazzi E, Schmitz L, Gulati A, von Cossel KM, Spiro A, Rupprecht M, Stuecker R, Muschol NM
J Orthop Surg Res 2021 Mar 19;16(1):201. doi: 10.1186/s13018-021-02340-6. PMID: 33741007Free PMC Article
van den Broek BTA, Smit AL, Boelens JJ, van Hasselt PM
J Inherit Metab Dis 2020 Nov;43(6):1279-1287. Epub 2020 Jul 9 doi: 10.1002/jimd.12277. PMID: 32579781Free PMC Article
Dohrmann T, Muschol NM, Sehner S, Punke MA, Haas SA, Roeher K, Breyer S, Koehn AF, Ullrich K, Zöllner C, Petzoldt M
Paediatr Anaesth 2020 Feb;30(2):181-190. Epub 2020 Jan 27 doi: 10.1111/pan.13787. PMID: 31834659
Bilginer Gurbuz B, Aypar E, Coskun T, Alehan D, Dursun A, Tokatli A, Sivri HS
J Pediatr Endocrinol Metab 2019 Oct 25;32(10):1049-1053. doi: 10.1515/jpem-2019-0293. PMID: 31469658
Khan SA, Peracha H, Ballhausen D, Wiesbauer A, Rohrbach M, Gautschi M, Mason RW, Giugliani R, Suzuki Y, Orii KE, Orii T, Tomatsu S
Mol Genet Metab 2017 Jul;121(3):227-240. Epub 2017 May 26 doi: 10.1016/j.ymgme.2017.05.016. PMID: 28595941Free PMC Article

Diagnosis

Breyer SR, Vettorazzi E, Schmitz L, Gulati A, von Cossel KM, Spiro A, Rupprecht M, Stuecker R, Muschol NM
J Orthop Surg Res 2021 Mar 19;16(1):201. doi: 10.1186/s13018-021-02340-6. PMID: 33741007Free PMC Article
van den Broek BTA, Smit AL, Boelens JJ, van Hasselt PM
J Inherit Metab Dis 2020 Nov;43(6):1279-1287. Epub 2020 Jul 9 doi: 10.1002/jimd.12277. PMID: 32579781Free PMC Article
Arunkumar N, Langan TJ, Stapleton M, Kubaski F, Mason RW, Singh R, Kobayashi H, Yamaguchi S, Suzuki Y, Orii K, Orii T, Fukao T, Tomatsu S
J Hum Genet 2020 Jul;65(7):557-567. Epub 2020 Apr 10 doi: 10.1038/s10038-020-0744-8. PMID: 32277174
Dohrmann T, Muschol NM, Sehner S, Punke MA, Haas SA, Roeher K, Breyer S, Koehn AF, Ullrich K, Zöllner C, Petzoldt M
Paediatr Anaesth 2020 Feb;30(2):181-190. Epub 2020 Jan 27 doi: 10.1111/pan.13787. PMID: 31834659
Bilginer Gurbuz B, Aypar E, Coskun T, Alehan D, Dursun A, Tokatli A, Sivri HS
J Pediatr Endocrinol Metab 2019 Oct 25;32(10):1049-1053. doi: 10.1515/jpem-2019-0293. PMID: 31469658

Therapy

Shukla P, Dvorak CC, Long-Boyle J, Kharbanda S
Int J Mol Sci 2020 Aug 6;21(16) doi: 10.3390/ijms21165634. PMID: 32781600Free PMC Article
Bilginer Gurbuz B, Aypar E, Coskun T, Alehan D, Dursun A, Tokatli A, Sivri HS
J Pediatr Endocrinol Metab 2019 Oct 25;32(10):1049-1053. doi: 10.1515/jpem-2019-0293. PMID: 31469658
Kang R, Shin YH, Gil NS, Oh YN, Hahm TS, Jeong JS
Paediatr Anaesth 2018 Dec;28(12):1116-1122. Epub 2018 Oct 29 doi: 10.1111/pan.13514. PMID: 30375140
Laoharawee K, Podetz-Pedersen KM, Nguyen TT, Evenstar LB, Kitto KF, Nan Z, Fairbanks CA, Low WC, Kozarsky KF, McIvor RS
Hum Gene Ther 2017 Aug;28(8):626-638. Epub 2017 May 5 doi: 10.1089/hum.2016.184. PMID: 28478695
Wang J, Luan Z, Jiang H, Fang J, Qin M, Lee V, Chen J
Biol Blood Marrow Transplant 2016 Nov;22(11):2104-2108. Epub 2016 Aug 20 doi: 10.1016/j.bbmt.2016.08.015. PMID: 27555533

Prognosis

van den Broek BTA, Smit AL, Boelens JJ, van Hasselt PM
J Inherit Metab Dis 2020 Nov;43(6):1279-1287. Epub 2020 Jul 9 doi: 10.1002/jimd.12277. PMID: 32579781Free PMC Article
Dohrmann T, Muschol NM, Sehner S, Punke MA, Haas SA, Roeher K, Breyer S, Koehn AF, Ullrich K, Zöllner C, Petzoldt M
Paediatr Anaesth 2020 Feb;30(2):181-190. Epub 2020 Jan 27 doi: 10.1111/pan.13787. PMID: 31834659
Bilginer Gurbuz B, Aypar E, Coskun T, Alehan D, Dursun A, Tokatli A, Sivri HS
J Pediatr Endocrinol Metab 2019 Oct 25;32(10):1049-1053. doi: 10.1515/jpem-2019-0293. PMID: 31469658
Teär Fahnehjelm K, Olsson M, Chen E, Hengstler J, Naess K, Winiarski J
Acta Paediatr 2018 Nov;107(11):1995-2003. Epub 2018 May 23 doi: 10.1111/apa.14368. PMID: 29683519
Khan SA, Peracha H, Ballhausen D, Wiesbauer A, Rohrbach M, Gautschi M, Mason RW, Giugliani R, Suzuki Y, Orii KE, Orii T, Tomatsu S
Mol Genet Metab 2017 Jul;121(3):227-240. Epub 2017 May 26 doi: 10.1016/j.ymgme.2017.05.016. PMID: 28595941Free PMC Article

Clinical prediction guides

Breyer SR, Vettorazzi E, Schmitz L, Gulati A, von Cossel KM, Spiro A, Rupprecht M, Stuecker R, Muschol NM
J Orthop Surg Res 2021 Mar 19;16(1):201. doi: 10.1186/s13018-021-02340-6. PMID: 33741007Free PMC Article
van den Broek BTA, Smit AL, Boelens JJ, van Hasselt PM
J Inherit Metab Dis 2020 Nov;43(6):1279-1287. Epub 2020 Jul 9 doi: 10.1002/jimd.12277. PMID: 32579781Free PMC Article
Dohrmann T, Muschol NM, Sehner S, Punke MA, Haas SA, Roeher K, Breyer S, Koehn AF, Ullrich K, Zöllner C, Petzoldt M
Paediatr Anaesth 2020 Feb;30(2):181-190. Epub 2020 Jan 27 doi: 10.1111/pan.13787. PMID: 31834659
Lee CL, Lin HY, Chuang CK, Chiu HC, Tu RY, Huang YH, Hwu WL, Tsai FJ, Chiu PC, Niu DM, Chen YJ, Chao MC, Chang TM, Lin JL, Chang CY, Kao YC, Lin SP
Mol Genet Genomic Med 2019 Aug;7(8):e790. Epub 2019 Jun 18 doi: 10.1002/mgg3.790. PMID: 31215158Free PMC Article
Kadali S, Patlolla RD, Kolusu A, Undamatla KT, Gummadi MR, Undamatla J
Clin Chim Acta 2016 Jun 1;457:36-40. Epub 2016 Mar 17 doi: 10.1016/j.cca.2016.03.007. PMID: 26995660

Recent systematic reviews

da Silva EM, Strufaldi MW, Andriolo RB, Silva LA
Cochrane Database Syst Rev 2016 Feb 5;2:CD008185. doi: 10.1002/14651858.CD008185.pub4. PMID: 26845288Free PMC Article
Angelis A, Tordrup D, Kanavos P
Health Policy 2015 Jul;119(7):964-79. Epub 2014 Dec 30 doi: 10.1016/j.healthpol.2014.12.016. PMID: 25661982
da Silva EM, Strufaldi MW, Andriolo RB, Silva LA
Cochrane Database Syst Rev 2014 Jan 8;(1):CD008185. doi: 10.1002/14651858.CD008185.pub3. PMID: 24399699
Cui Y, Zhao H, Liu Z, Liu C, Luan J, Zhou X, Han J
Orphanet J Rare Dis 2012 Aug 22;7:55. doi: 10.1186/1750-1172-7-55. PMID: 22913777Free PMC Article
da Silva EM, Strufaldi MW, Andriolo RB, Silva LA
Cochrane Database Syst Rev 2011 Nov 9;(11):CD008185. doi: 10.1002/14651858.CD008185.pub2. PMID: 22071845

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