Sly syndrome
{{Infobox medical condition (new)
| synonyms = β-glucuronidase deficiency, β-glucuronidase deficiency mucopolysaccharidosis,
| name = Sly syndrome
| image = autorecessive.svg
| caption = Sly syndrome has an autosomal recessive pattern of inheritance.
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Sly syndrome, also called mucopolysaccharidosis type VII (MPS-VII), is an autosomal recessive lysosomal storage disease caused by a deficiency of the enzyme β-glucuronidase. This enzyme is responsible for breaking down large sugar molecules called glycosaminoglycans (AKA GAGs, or mucopolysaccharides). The inability to break down GAGs leads to a buildup in many tissues and organs of the body. The severity of the disease can vary widely.{{Cite web |date=25 June 2019 |title=Mucopolysaccharidosis type VII |url=https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-vii |access-date=2 July 2019 |publisher=United States National Library of Medicine}}
Signs and symptoms
The most severe cases of Sly syndrome can result in hydrops fetalis, which results in fetal death or death soon after birth. Some people with Sly syndrome may begin to have symptoms in early childhood. Symptoms can include an enlarged head, fluid buildup in the brain, coarse facial features, enlarged tongue, enlarged liver, enlarged spleen, problems with the heart valves, and abdominal hernias. People with Sly syndrome may also have sleep apnea, frequent lung infections, and problems with vision secondary to cloudy corneas. Sly syndrome causes various musculoskeletal abnormalities that worsen with age. These can include short stature, joint deformities, dysostosis multiplex, spinal stenosis, and carpal tunnel syndrome.
While some individuals have developmental delay, others may have normal intelligence. However, the accumulation of GAGs in the brain usually leads to the slowing of development from ages 1–3, and then a loss of previously learned skills until death.
Genetics
The defective gene responsible for Sly syndrome is located on chromosome 7.{{Cite journal |last=Allanson |first=JE |last2=Gemmill |first2=RM |last3=Hecht |first3=BK |last4=Johnsen |first4=S |last5=Wenger |first5=DA |year=1988 |title=Deletion mapping of the beta-glucuronidase gene. |journal=American Journal of Medical Genetics |volume=29 |issue=3 |pages=517–522 |doi=10.1002/ajmg.1320290307 |pmid=3376995}}
Diagnosis
Most people with Sly disease will have elevated levels of GAGs seen in the urine. A confirmatory test is necessary for diagnosis. Skin cells and red blood cells of affected people will have low levels of β-glucuronidase activity. Sly syndrome can also be diagnosed through prenatal testing.
Treatment
Vestronidase alfa-vjbk (trade name Mepsevii), an enzyme replacement therapy which is a recombinant form of human β-glucuronidase, is approved by U.S. Food and Drug Administration for the treatment of Sly syndrome.{{Cite journal |last=McCafferty |first=EH |last2=Scott |first2=LJ |date=April 2019 |title=Vestronidase alfa: A review in mucopolysaccharidosis VII |journal=BioDrugs |volume=33 |issue=2 |pages=233–240 |doi=10.1007/s40259-019-00344-7 |pmc=6469592 |pmid=30848434 |doi-access=free}} Hematopoietic stem cell transplant (HSCT) has been used to treat other types of MPS diseases, but this is not yet available for MPS-VII. Animal experiments suggest that HSCT may be an effective treatment for MPS-VII in humans.
Prognosis
Epidemiology
History
Sly syndrome was originally discovered in 1972.{{Cite web |title=A Guide to Understanding MPS VII |url=https://mpssociety.org/cms/wp-content/uploads/2017/04/MPS_VII_2008.pdf |url-status=dead |archive-url=https://web.archive.org/web/20190703003006/https://mpssociety.org/cms/wp-content/uploads/2017/04/MPS_VII_2008.pdf |archive-date=3 July 2019 |access-date=2 July 2019 |publisher=National MPS Society}} It was named after its discoverer William S. Sly, an American biochemist who has spent nearly his entire academic career at Saint Louis University.{{Cite web |title=slu.edu |url=http://www.slu.edu/x14852.xml |url-status=dead |archive-url=https://web.archive.org/web/20070911152518/http://www.slu.edu/x14852.xml |archive-date=2007-09-11 |access-date=2007-12-31}}{{Cite journal |vauthors=Sly WS, Quinton BA, McAlister WH, Rimoin DL |year=1973 |title=Beta glucuronidase deficiency: report of clinical, radiologic, and biochemical features of a new mucopolysaccharidosis |journal=J. Pediatr. |volume=82 |issue=2 |pages=249–57 |doi=10.1016/S0022-3476(73)80162-3 |pmid=4265197}}
References
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{{Medical resources
| DiseasesDB = 8389
| ICD10 = {{ICD10|E|76|2|e|70}}
| ICD9 = {{ICD9|277.5}}
| ICDO =
| OMIM = 253220
| MedlinePlus =
| eMedicineSubj = ped
| eMedicineTopic = 858
| MeshID = D016538
|Orphanet=584|ICD11={{ICD11|5C56.3Y}}}}
{{Mucopolysaccharidoses}}
Category:Proteoglycan metabolism disorders
Category:Autosomal recessive disorders
Category:Skin conditions resulting from errors in metabolism