Summary about Disease
Beta-glucuronidase deficiency, also known as Sly syndrome or mucopolysaccharidosis type VII (MPS VII), is a rare, inherited metabolic disorder caused by a deficiency of the enzyme beta-glucuronidase. This enzyme is essential for breaking down complex carbohydrates called glycosaminoglycans (GAGs), also known as mucopolysaccharides. When the enzyme is deficient, GAGs accumulate in cells and tissues throughout the body, leading to a wide range of symptoms affecting multiple organ systems. The severity of MPS VII varies greatly, ranging from mild to severe.
Symptoms
Symptoms of beta-glucuronidase deficiency vary widely in severity and can include:
Skeletal abnormalities: Short stature, dysostosis multiplex (characteristic skeletal abnormalities seen on X-rays), joint stiffness, scoliosis.
Organomegaly: Enlarged liver (hepatomegaly) and spleen (splenomegaly).
Facial features: Coarse facial features, large tongue (macroglossia).
Hernias: Umbilical and inguinal hernias.
Heart problems: Heart valve abnormalities, cardiomyopathy.
Respiratory problems: Frequent respiratory infections, sleep apnea.
Neurological problems: Developmental delay, intellectual disability, hydrocephalus (fluid accumulation in the brain).
Hearing and vision problems: Hearing loss, corneal clouding.
Skin: Thickened skin.
Hydrops fetalis: In severe cases, can present as hydrops fetalis (fluid accumulation in multiple body cavities) leading to stillbirth or death shortly after birth.
Causes
Beta-glucuronidase deficiency is caused by mutations in the GUSB gene, which provides instructions for making the beta-glucuronidase enzyme. These mutations lead to a deficiency or absence of the functional enzyme. It is inherited in an autosomal recessive pattern. This means that an affected individual must inherit two copies of the mutated gene (one from each parent) to develop the disorder. Individuals who inherit only one copy of the mutated gene are carriers and typically do not show symptoms of the disorder.
Medicine Used
4. Medicine used
Enzyme replacement therapy (ERT): Vestronidase alfa (Mepsevii) is an enzyme replacement therapy approved for the treatment of non-neurological manifestations of MPS VII. It provides a functional version of the beta-glucuronidase enzyme to help break down accumulated GAGs.
Hematopoietic stem cell transplantation (HSCT): In some cases, HSCT has been used, particularly in individuals with more severe forms of the disease. This involves replacing the affected individual's bone marrow with healthy stem cells from a donor. It aims to provide a source of functional beta-glucuronidase.
Supportive care: Medications and therapies to manage specific symptoms, such as pain relief, physical therapy for joint stiffness, respiratory support, and treatments for heart problems.
Is Communicable
No, beta-glucuronidase deficiency (MPS VII) is not communicable. It is a genetic disorder caused by mutations in the GUSB gene and is inherited from parents to their offspring. It cannot be spread from person to person through infection or any other means.
Precautions
Precautions focus on managing symptoms and preventing complications. Specific precautions depend on the individual's symptoms and the severity of their condition. General precautions include:
Regular medical monitoring: Regular check-ups with specialists (e.g., geneticists, cardiologists, pulmonologists, orthopedists, ophthalmologists, audiologists) to monitor the progression of the disease and adjust treatment as needed.
Vaccinations: Following recommended vaccination schedules to prevent infections, as individuals with MPS VII may be more susceptible to respiratory infections.
Respiratory support: Taking precautions to avoid respiratory infections and seeking prompt treatment if they occur. Consider flu and pneumonia vaccines.
Physical therapy and occupational therapy: Engaging in regular physical and occupational therapy to maintain joint mobility, strength, and function.
Cardiac monitoring: Regular cardiac evaluations to monitor heart function and manage any heart problems.
Hearing and vision care: Regular hearing and vision tests to detect and manage any hearing loss or vision problems.
Anesthesia precautions: Informing medical professionals about the diagnosis of MPS VII before any surgical procedures or anesthesia, as there may be specific considerations related to airway management and other potential complications.
Genetic counseling: Genetic counseling for individuals with MPS VII and their families to understand the inheritance pattern of the disorder and the risk of recurrence in future pregnancies.
How long does an outbreak last?
Beta-glucuronidase deficiency is not an infectious disease, and thus it doesn't have outbreaks in the typical sense. The disease is chronic and lifelong. Symptoms may progress or fluctuate over time, but there are no outbreaks or periods of contagion. The disease is continuously present from early in life or at birth.
How is it diagnosed?
Diagnosis of beta-glucuronidase deficiency typically involves:
Clinical evaluation: Physical examination and assessment of symptoms, including skeletal abnormalities, organomegaly, facial features, and developmental delays.
Urine tests: Measuring the levels of GAGs in the urine. Elevated levels of GAGs may suggest a mucopolysaccharidosis disorder.
Enzyme assay: Measuring the activity of the beta-glucuronidase enzyme in blood leukocytes or cultured fibroblasts. Reduced or absent enzyme activity confirms the diagnosis.
Genetic testing: Analyzing the GUSB gene for mutations. Identifying two disease-causing mutations confirms the diagnosis.
Radiological studies: X-rays to assess skeletal abnormalities (dysostosis multiplex) and other imaging studies (e.g., MRI, CT scan) to evaluate organ involvement.
Timeline of Symptoms
The timeline of symptoms in beta-glucuronidase deficiency varies greatly depending on the severity of the condition:
Severe/Prenatal Form: Hydrops fetalis may be present prenatally, leading to stillbirth or death shortly after birth.
Infantile Form: Symptoms often appear in infancy or early childhood. Symptoms may include coarse facial features, organomegaly, skeletal abnormalities, developmental delay, and frequent respiratory infections.
Childhood/Adolescent Form: In milder cases, symptoms may not become apparent until later in childhood or adolescence. These individuals may have milder skeletal abnormalities, slower progression of developmental delays, and less severe organ involvement. The progression of symptoms can vary, and some individuals may experience a more rapid decline than others.
Important Considerations
Variability: The severity of beta-glucuronidase deficiency varies widely, even among individuals with the same genetic mutations.
Early diagnosis: Early diagnosis and treatment are crucial to managing the symptoms and improving the long-term outcome.
Multidisciplinary care: Management requires a multidisciplinary team of specialists, including geneticists, cardiologists, pulmonologists, orthopedists, ophthalmologists, and therapists.
Genetic counseling: Genetic counseling is important for families to understand the inheritance pattern and recurrence risk.
Research: Ongoing research is focused on developing new and improved treatments for MPS VII.