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Genetics of Mucopolysaccharidosis Type VII

  • Author: Maryam Banikazemi, MD; Chief Editor: Maria Descartes, MD  more...
Updated: Nov 10, 2015


The mucopolysaccharidoses (MPSs) are a group of inherited lysosomal storage disorders that are caused by a deficiency of specific lysosomal enzymes required for the degradation of glycosaminoglycans (GAGs) (mucopolysaccharides). MPSs show extensive genetic heterogeneity, both among and within loci.

Mucopolysaccharidosis type VII (MPS VII) is a very rare lysosomal storage disease. MPS VII, traditionally known as Sly syndrome, was characterized for the first time in a patient with skeletal features similar to those observed in other patients with MPS. Sly syndrome is caused by deficiency of the enzyme β -glucuronidase.[1] Historically, MPS VII is of interest because it was the first MPS (excluding the sex-linked gene for Hunter syndrome) for which the mutant gene was localized to chromosome 7.



In MPS VII the molecular defect on the gene that encodes β-glucuronidase protein (GUSB) leads to deficiency of the enzyme β-glucuronidase. This enzyme is required for the breakdown of several GAGs, including dermatan sulfate (DS), heparan sulfate (HS), and chondroitin sulfate (CS).[2] Accumulation of DS, HS, and CS takes place in the lysosome of many systems and tissues, including the CNS. The pattern of urinary excretion of HS, DS, and/or CS may vary based on the subtype of MPS VII involved.


The GUSB is located on chromosome 7q11.21-7q11.22, is 21-kb long, and contains 12 exons. The defect in GUSB is responsible for Sly syndrome. More than 45 mutation different mutations have been identified, approximately 90% of which were point mutations. The limited data reflect the severity of disease in part can be attributed to the genotype and residual catalytic enzyme activity.




United States

MPS VII is extremely rare, and few cases have been described.


In his extensive study of MPSs in Northern Ireland in 1997, Nelson reported that no living cases of MPS VII were observed from 1958-1985. Three cases of nonimmune hydrops fetalis were believed to be MPS VII on the basis of placental histology and enzyme studies in the parents.[3]


Only a small sample of cases is available from which to extrapolate mortality figures for MPS VII. Fetal deaths have been noted several times. In mild cases, survival to age 19-20 years has been reported. Upper respiratory tract infections, neurodegenerative complications, and GI tract conditions may contribute to reduced survival rates.


Males and females are affected in equal numbers. Transmission is autosomal recessive.


As a point of emphasis, Sly syndrome is one of the few MPSs and lysosomal storage diseases that may be clinically evident at birth, and even the most severe defects may appear prenatally. In other forms, defects may present during the first years of life. In the milder forms, clinical features may not be evident until later.

Contributor Information and Disclosures

Maryam Banikazemi, MD Assistant Professor of Clinical Pediatrics, New York Medical College

Maryam Banikazemi, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.


Surendra Varma, MD, FAAP, FACE, DSc(Hon) Associate Dean for Graduate Medical Education and Resident Affairs, Ted Hartman Endowed Chair in Medical Education, University Distinguished Professor and Vice-Chair of Pediatrics, Professor of Physiology and Health Organization Management, Program Director Emeritus, Pediatric Residency Program, Texas Tech University Health Sciences Center School of Medicine

Surendra Varma, MD, FAAP, FACE, DSc(Hon) is a member of the following medical societies: Alpha Omega Alpha, Academic Pediatric Association, American Association of Clinical Endocrinologists, American Pediatric Society, Society for Pediatric Research, American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Sigma Xi, Texas Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Margaret M McGovern, MD, PhD Professor and Chair of Pediatrics, Stony Brook University School of Medicine

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Karl S Roth, MD Retired Professor and Chair, Department of Pediatrics, Creighton University School of Medicine

Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.


The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Donald Nash, MD, to the development and writing of this article.

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