Acknowledgement of Mucopolysaccharidosis Type VII (Sly Syndrome) has not been added yet.

MPS VII is an extremely rare disorder, with an estimated prevalence of 1 in 250,000 to 1 in 1,000,000 live births. The condition is found worldwide but is particularly noted in certain populations, including those of Ashkenazi Jewish descent, where the incidence may be higher. Due to its rarity, awareness and understanding of the condition can be limited, which may affect timely diagnosis and treatment.

Name	Abbreviation
Beta-glucuronidase Deficiency
Sly Syndrome	MPS VII

MPS VII is caused by pathogenic variants in the GUSB gene, located on chromosome 7 (7q21.11). This gene encodes the enzyme beta-glucuronidase, which is responsible for breaking down the GAGs chondroitin sulfate, dermatan sulfate and heparan sulfate. This results in their accumulation in cellular compartments called lysosomes, leading to cellular dysfunction, tissue damage and a wide array of clinical symptoms.

The clinical presentation of MPS VII can vary widely, with manifestations ranging from severe forms evident at birth to milder forms diagnosed in adulthood. Common symptoms include:

• Coarse Facial Features:  Such as a broad nose, thick lips and prominent forehead.

• Skeletal Abnormalities:  Such as short stature or dysostosis multiplex, which involves abnormal bone development.

• Joint Stiffness:  Limited mobility and discomfort in joints.

• Hepatosplenomegaly:  Enlargement of the liver and spleen.

• Corneal Clouding:  Opacity in the cornea, affecting vision.

• Hearing Loss:  Progressive impairment often due to structural changes and recurrent ear infections.

• Cardiac Abnormalities:  Issues with heart function and structure.

• Respiratory Problems:  Airway obstruction due to enlarged tonsils and adenoids.

• Intellectual Disability:  Cognitive impairment may occur in some individuals.

• Hydrops Fetalis:  Severe cases of fluid buildup in fetal tissues and organs during pregnancy.

The diagnosis of MPS VII is based on clinical suspicion supported by biochemical and genetic testing. Key diagnostic steps may include:

• Clinical Evaluation:  Assessment of symptoms and physical characteristics.

• Urine GAG Analysis:  Testing for elevated levels of the GAGs chondroitin sulfate, dermatan sulfate and heparan sulfate.

• Enzyme Activity Assay:  Measurement of beta-glucuronidase activity in leukocytes, fibroblasts or dried blood spots.

• Genetic Testing: Identification of pathogenic variants in the GUSB gene.

• Imaging Studies:  X-rays or MRI can evaluate skeletal abnormalities and organ size.

• Echocardiogram:  To assess cardiac function.

• Ophthalmological Exam:  To evaluate corneal clouding and other eye abnormalities.

• Hearing Tests

• Developmental and Cognitive Assessments

• Prenatal Testing for at-risk pregnancies

Diagnostic tests of Mucopolysaccharidosis Type VII (Sly Syndrome) has not been added yet

Currently, there is no cure for MPS VII. Treatment focuses on alleviating symptoms and improving quality of life:

• Enzyme Replacement Therapy (ERT): Vestronidase alfa, a recombinant human beta-glucuronidase, is FDA-approved for replacing the deficient enzyme.

• Supportive Care: Management of specific symptoms, including:

  • Physical, occupational and speech therapy.

  • Respiratory support.

  • Cardiac monitoring and interventions.

  • Orthopedic care for skeletal issues.

  • Hearing and vision aids.

• Hematopoietic Stem Cell Transplantation (HSCT): May be considered in some cases, although its efficacy is not well established for MPS VII.

• Emerging Therapies: Research is ongoing for potential treatments such as gene therapy and substrate reduction therapy.

The prognosis for individuals with MPS VII varies significantly based on disease severity. Those with milder forms may survive into adulthood, while those having severe infantile or childhood forms often have a substantially shortened lifespan. Early diagnosis and comprehensive management can improve the quality of life and potentially slow disease progression.

The introduction of enzyme replacement therapy may improve outcomes and quality of life for some patients, but long-term data are still being collected.

 

Tips or Suggestions of Mucopolysaccharidosis Type VII (Sly Syndrome) has not been added yet.

1. Montaño, A. M., et al. (2016). “Clinical Course of Sly Syndrome (Mucopolysaccharidosis Type VII).” J Medical Gen, 53(6), 403-418.

2. Wang, R.Y., et al. (2020). “The Long-term Safety and Efficacy of Vestronidase Alfa, rhGUS Enzyme Replacement Therapy, in Subjects with Mucopolysaccharidosis VII.” Mol Genet Metab, 129(3), 219-227.

3. Zielonka, M., Garbade, S. F., Kölker, S., Hoffmann, G. F., & Ries, M. (2017). “Quantitative Clinical Characteristics of 53 patients with MPS VII: A Cross-sectional Analysis.” Genet Med, 19(9), 983-988.

4. Orphanet:  Mucopolysaccharidosis Type 7.

5. PubMed: Mucopolysaccharidosis Type VII

6. NORD (National Organization for Rare Disorders): Mucopolysaccharidosis Type VII.