Sly Syndrome (Mucopolysaccharidosis Type VII) Treatment & Management

Updated: Nov 30, 2017
  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD  more...
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Treatment

Medical Care

Supportive care

Prognosis is poor for antenatal forms of Sly syndrome (mucopolysaccharidosis type VII [MPS VII]), most often leading to death in utero. Neonatal and childhood forms have a very limited life expectancy, whereas milder forms have a greater prolonged survival.

As in some other MPS types, symptomatic treatment is essential for survival of patients with milder cases and late-onset forms. Although the available medical and surgical interventions do not address the underlying cause of the disease or reverse/arrest the progression of the disease, these approaches may greatly improve the quality of life for both patients and their families.

The symptomatic intervention for Sly syndrome includes, but is not limited to, treatment and management of CNS anomalies, respiratory and cardiovascular complications, auditory and visual impairments, gastrointestinal symptoms, skeletal manifestations, and arthropathies.

Disease-specific treatment

Treatment that directly targets the underlying cause of the disease and prevents accumulation of substrate is in development for several inherited metabolic storage disorders. Promising studies are underway in various animal models of Sly syndrome (eg, mutant mice, [7] cats, dogs). These approaches include the following:

  • Bone marrow or cord blood transplantation, which endogenously restores production of the missing functional enzyme. [8]
  • Enzyme replacement therapy (ERT), which supplements exogenously deficient enzyme production via recombinant DNA technology. [9]
  • Gene transfer and modified fibroblast implants that supply the patient with a functional gene to produce the deficient enzyme.

Enzyme replacement therapy

The US Food and Drug Administration (FDA) has approved vestronidase alfa-vjbk (Mepsevii) for the treatment of Sly syndrome (mucopolysaccharidosis type VII [MPS VII]) in pediatric and adult patients. This enzyme replacement therapy is intended to replace the deficient lysosomal enzyme beta-glucuronidase in patients with Sly syndrome. Approval was based on a clinical trial program that included 23 patients with MPS VII; the patients ranged in age from 5 months to 25 years. Patients received vestronidase alfa-vjbk at doses up to 4 mg/kg IV every 2 weeks for up to 164 weeks. Efficacy was primarily assessed through the 6-minute walk test (6MWT) in 10 patients who could perform the test.

After 24 weeks, the mean difference in distance walked relative to placebo was 18 meters. Additional follow-up for up to 120 weeks suggested continued improvement in 3 patients and stabilization in the remaining 7 patients. After 120 weeks of exposure, one patient demonstrated a 21% improvement over baseline in forced vital capacity (FVC% predicted) on pulmonary function testing in addition to a 105-meter improvement in the 6MWT. Two other patients with baseline hepatosplenomegaly had reduction in liver volume (24% and 53%) and spleen volume (28% and 47%) after 36 weeks of treatment. The effect of vestronidase alfa-vjbk on the CNS manifestations of MPS VII has not been determined. [10]

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Surgical Care

Corrective surgery may be necessary in patients with joint contractures and other skeletal abnormalities.

Corneal transplants may be required if problems in vision become severe.

Patients with Sly syndrome (MPS VII) have sensitivity to anesthesia. Postsurgical pulmonary complications can occur.

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Consultations

Patients with Sly syndrome require referral to a pediatrician and a pediatric neurologist, ophthalmologist, audiologist, cardiologist, gastroenterologist, orthopedic surgeon, and general surgeon. Consider referrals to developmental pediatrics and physical therapy.

Refer patients and their families to medical geneticists for diagnosis and genetic counseling.

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