Sly syndrome

Sly Syndrome Signs and Symptoms

Sly syndrome, also known as Mucopolysaccharidosis type VII (MPS VII), is a progressive condition that affects most tissues and organs. The severity of the condition can vary, but it typically begins to show signs and symptoms during early childhood.

Common Symptoms:

• Enlarged head (macrocephaly)
• Build-up of fluid in the brain (hydrocephalus)
• Coarse facial features
• Enlarged tongue (macroglossia)
• Umbilical hernia or inguinal hernia
• Arthritis
• Carpal tunnel syndrome
• Joint contractures

Severe Cases:

• Hydrops fetalis, which can result in fetal death or death soon after birth
• Neonatal jaundice or yellowing of the skin

Progressive Symptoms:

• Hip dysplasia
• Worsening pulmonary function
• Short stature (height significantly shorter than average)
• Joint deformities that affect mobility
• Dysostosis multiplex (abnormal bone development)

These symptoms can vary in severity and may become more pronounced with age. It's essential to note that each individual with Sly syndrome may experience a unique set of symptoms, and the progression of the condition can differ from person to person.

References:

• [1] The most severe cases of MPS VII are characterized by hydrops fetalis, or when excess fluid accumulates in the body before birth. This can result in a stillborn or death shortly after birth.
• [2-5] Symptoms of less severe forms of MPS VII may appear during early childhood and include an enlarged head, fluid buildup in the brain, coarse facial features, enlarged tongue, umbilical hernia or inguinal hernia, arthritis, carpal tunnel syndrome, joint contractures, hip dysplasia, worsening pulmonary function, short stature, joint deformities that affect mobility, and dysostosis multiplex.
• [6-9] The most common presenting symptoms include generalized weakness, malaise, arthralgias, abdominal pain, and impotence (in men). Physical examination may reveal a large head, fluid buildup in the brain, distinctive-looking facial features, macrocephaly, hydrocephalus, coarse facial features, macroglossia, enlarged liver, enlarged spleen, problems with the heart valves, and abdominal hernias.

Diagnostic Tests for Sly Syndrome (MPS VII)

Sly syndrome, also known as mucopolysaccharidosis type VII (MPS VII), is a rare lysosomal storage disease that requires accurate diagnosis to ensure proper treatment and management. The following diagnostic tests are used to confirm the presence of MPS VII:

• Biochemical testing: This involves measuring the level of beta-glucuronidase enzyme activity in blood or skin cells. A deficiency in this enzyme is considered the gold standard for diagnosing MPS VII [2].
• Genetic testing: Molecular testing can be used to confirm the diagnosis and identify disease-causing mutations within a family, allowing for carrier testing and prenatal diagnosis [11].
• Clinical evaluation: A thorough clinical evaluation, including a detailed patient history and specialized tests, is necessary to confirm the diagnosis of MPS VII [1, 8].
• Specialized blood tests: Tests that measure the level of beta-glucuronidase enzyme activity in blood cells are used to diagnose MPS VII [9].
• Urine tests: Urinary GAG excretion tests can suggest the presence of MPS VII through clinical examination and urine tests for excess glycosaminoglycan (GAG) excretion [9].

Important Considerations

It's essential to note that diagnostic testing and screening for MPS are not currently standardized, so open communication between laboratories and physicians is necessary to facilitate the interpretation of specific diagnostic tests and results [4]. Additionally, all diagnostic tests should be overseen by a doctor with expertise in lysosomal storage diseases (LSDs), as the tests are complicated and results may be difficult to interpret [13].

References

[1] Steiner, RD, et al. Clinical course of sly syndrome (mucopolysaccharidosis type VII). J. Med. Genet. 2016;53, 403-418.

[2] This biochemical test is a quantitative measurement of beta-glucuronidase enzyme activity and can be used as a 1st tier test for patients with a clinical suspicion of Mucopolysaccharidosis VII [2].

[3] Molecular testing is useful to confirm the diagnosis and to identify the disease-causing mutations within a family to allow for carrier testing and prenatal diagnosis [11].

[4] Diagnostic tests should be overseen by a doctor with expertise in LSDs, as the tests are complicated and results may be difficult to interpret [13].

Treatment Options for Sly Syndrome

Sly syndrome, also known as Mucopolysaccharidosis Type VII (MPS VII), is a rare genetic disorder caused by the lack of the enzyme beta-glucuronidase. While there is no cure for this condition, various treatment options are available to manage its symptoms and improve quality of life.

Enzyme Replacement Therapy

One of the most promising treatments for Sly syndrome is Enzyme Replacement Therapy (ERT). ERT involves administering a recombinant human enzyme that replaces the deficient beta-glucuronidase in patients. This therapy has been shown to provide clinically important benefits, such as improved pulmonary function and walking ability, reduced excess carbohydrates stored in the body, and overall improvement in quality of life [5][6].

Specific Treatment Options

• Vestronidase alfa-vjbk (Mepsevii) is a FDA-approved ERT for the treatment of Sly syndrome in pediatric and adult patients [14]. This enzyme replacement therapy is intended to replace the deficient lysosomal enzyme beta-glucuronidase in patients with Sly syndrome.
• Experimental ERT has also been used to treat patients with Sly syndrome, such as infusing recombinant human beta-glucuronidase at 2mg/kg over 4h every 2 weeks for 24 weeks [7].

Other Treatment Options

While ERT is a promising treatment option, other supportive treatments are also available to manage the symptoms of Sly syndrome. These may include physical therapy, occupational therapy, and pain management.

References:

• [1] Patients received treatment with Mepsevii at doses up to 4 mg/kg once every two weeks for up to 164 weeks.
• [5] Enzyme replacement therapy may provide clinically important benefits (eg, improved pulmonary function and walking ability, reduced excess carbohydrates stored in the body).
• [6] Vestronidase alfa-vjbk injection is used to treat Mucopolysaccharidosis VII (MPS VII) or Sly syndrome.
• [7] Experimental ERT by infusing rhGUS at 2mg/kg over 4h every 2 weeks for 24 weeks.
• [14] The US Food and Drug Administration (FDA) has approved vestronidase alfa-vjbk (Mepsevii) for the treatment of Sly syndrome in pediatric and adult patients.

Understanding Differential Diagnosis for Sly Syndrome

Sly syndrome, also known as mucopolysaccharidosis type VII (MPS VII), is a rare lysosomal storage disease characterized by the deficiency of β-glucuronidase enzyme. When diagnosing Sly syndrome, it's essential to consider differential diagnoses that can mimic its symptoms.

Key Differential Diagnoses:

• Other types of mucopolysaccharidoses (MPS) and oligosaccharidoses
• Lysosomal storage diseases
• Metabolic disorders

Symptoms Overlap:

The symptoms of Sly syndrome, such as short stature, skeletal dysplasia, hepatosplenomegaly, hernias, cardiac involvement, pulmonary insufficiency, and cognitive impairment, can overlap with those of other conditions. A comprehensive diagnostic approach is necessary to rule out these differential diagnoses.

Diagnostic Considerations:

• Genetic testing for the GUSB gene mutation
• Enzymatic activity assays in leucocytes
• Imaging studies (e.g., X-rays, CT scans) to assess skeletal and organ involvement

Accurate Diagnosis:

A precise diagnosis of Sly syndrome requires a multidisciplinary approach, involving geneticists, pediatricians, neurologists, and other specialists. Early recognition and treatment can significantly improve the quality of life for individuals with this condition.

References:

• Zhou J, Lin J, Leung WT, Wang L. A basic understanding of mucopolysaccharidosis: Incidence, clinical features, diagnosis, and management.
• Henriques Nehm J, Kubaski F, Poletto E, Giugliani R. Diagnosis and Emerging Treatment Strategies for Mucopolysaccharidosis VII (Sly Syndrome).
• Van Dorpe J, Moerman P, Pecceu A, Van den Steen P, Fryns JP. Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly syndrome).