mucopolysaccharidosis VI

Mucopolysaccharidosis Type VI (MPS VI): A Rare Genetic Disorder

Mucopolysaccharidosis type VI, also known as Maroteaux-Lamy syndrome, is a rare genetic disorder caused by the deficiency of an enzyme called arylsulfatase B (ARSB). This enzyme plays a crucial role in breaking down large sugar molecules called glycosaminoglycans (GAGs), specifically dermatan sulfate and chondroitin sulfate.

Key Features:

• Progressive multisystem involvement: MPS VI affects multiple systems in the body, including the skeletal, nervous, and respiratory systems.
• Skeletal abnormalities: Patients with MPS VI often experience skeletal abnormalities, such as a large head (macrocephaly), hydrocephalus, and inguinal or umbilical hernias.
• Enlarged tissues and organs: The condition causes many tissues and organs to enlarge, become inflamed or scarred, and eventually waste away (atrophy).
• Inherited disorder: MPS VI is an inherited disease caused by a deficiency in the ARSB enzyme, which is responsible for breaking down dermatan sulfate and chondroitin sulfate.

Symptoms:

• Retarded growth
• Dysostosis multiplex (abnormal bone development)
• Inguinal or umbilical hernias
• Hydrocephalus (fluid buildup in the brain)
• Macrocephaly (large head)

Causes and Risk Factors:

• Genetic variations: MPS VI is caused by genetic variations that disrupt the normal activity of lysosomes in human cells.
• Inherited recessive disease: The condition is inherited as an autosomal recessive trait, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disorder.

References:

• [1] Mucopolysaccharidosis type VI (MPS VI) is when genetic variations disrupt the normal activity of lysosomes in human cells. Learn more from Boston ...
• [3] Maroteaux–Lamy syndrome, or Mucopolysaccharidosis Type VI (MPS-VI), is an inherited disease caused by a deficiency in the enzyme arylsulfatase B (ARSB).
• [7] MPS VI causes various skeletal abnormalities, including a large head (macrocephaly) with a buildup of fluid in the brain (hydrocephalus), ...
• [9] MPS VI is a genetic recessive disease caused by a deficiency in a specific enzyme, arylsulfatase B coded by the ARSB gene.

Mucopolysaccharidosis type VI (MPS VI), also known as Maroteaux-Lamy syndrome, is a progressive condition that causes many tissues and organs to enlarge, become inflamed or scarred, and eventually waste away (atrophy) [1]. The features of MPS VI affect many bodily systems, including the skeletal, respiratory, gastrointestinal, and cardiovascular systems.

Some common signs and symptoms of MPS VI include:

• Skeletal abnormalities: Short stature, stiff joints, and bone deformities are common in individuals with MPS VI [5].
• Respiratory problems: Breathing difficulties and lung problems are also prevalent in people with MPS VI [6].
• Coarse facial features: Individuals with MPS VI often have distinctive "coarse" facial features, which can be a characteristic sign of the condition [4].
• Organ enlargement: The liver and spleen may become enlarged due to the accumulation of mucopolysaccharides [6].
• Heart valve abnormalities: Heart problems, including valve abnormalities, are also associated with MPS VI [6].

In addition to these physical symptoms, individuals with MPS VI may experience a range of other complications, including spinal cord damage, which can lead to back pain and loss of bladder and bowel control [7]. Early diagnosis of MPS VI is crucial for managing the condition effectively.

References:

[1] Context 1: Mucopolysaccharidosis type VI (MPS VI), also known as Maroteaux-Lamy syndrome, is a progressive condition that causes many tissues and organs to enlarge, become inflamed or scarred, and eventually waste away (atrophy).

[4] Context 4: Signs & Symptoms. Individuals with MPS disorders share many similar symptoms such as multiple organ involvement, distinctive “coarse” facial features, and abnormalities of the skeleton especially joint problems.

[5] Context 5: Mucopolysaccharidosis type VI Description Mucopolysaccharidosis type VI (MPS VI), also known as Maroteaux-Lamy syndrome, is a progressive condition that causes many tissues and organs to enlarge, become inflamed or scarred, and eventually waste away (atrophy). Skeletal abnormalities are also common in this condition.

[6] Context 6: Patients with MPS VI have bone abnormalities, severe short stature, corneal clouding, lung problems, liver and spleen enlargement and heart valve abnormalities.

[7] Context 7: Spinal cord damage may occur due to the natural MPS VI disease process.

Diagnostic Tests for Mucopolysaccharidosis VI

Mucopolysaccharidosis VI (MPS VI) is a rare genetic disorder that affects the body's ability to break down and recycle sugar molecules. Accurate diagnosis is crucial for effective management and treatment of the disease.

• Urine Test: A urine test, specifically the toluidine blue-spot test, is often used as an initial screening tool for MPS VI. If the results are positive, further genetic testing may be required to confirm the diagnosis [6].
• Enzyme Assay: An enzyme assay is a definitive diagnostic test that measures the amount of an enzyme (called ASB) in a person's skin or blood cells. This test can help confirm the presence of MPS VI and distinguish it from other types of mucopolysaccharidoses [4].
• Urinary Glycosaminoglycan (uGAG) Analysis: This test measures the levels of glycosaminoglycans in the urine, which can be elevated in individuals with MPS VI. However, this test is not specific to MPS VI and may require further testing to confirm the diagnosis [12].
• Molecular Testing: Molecular testing involves analyzing DNA samples to identify genetic mutations associated with MPS VI. This type of testing can provide a definitive diagnosis and help distinguish MPS VI from other types of mucopolysaccharidoses [12].

Additional Diagnostic Tools

• Imaging Studies: Imaging studies, such as magnetic resonance imaging (MRI), may be used to evaluate spinal involvement in MPS VI [15].
• Clinical Evaluation: A thorough clinical evaluation by a healthcare professional experienced in lysosomal diseases is essential for accurate diagnosis and management of MPS VI.

It's essential to note that diagnostic tests for MPS VI should be overseen by a doctor with expertise in lysosomal diseases, as the tests are complicated and results may be difficult to interpret [7].

Treatment Options for Mucopolysaccharidosis Type VI

Mucopolysaccharidosis Type VI (MPS VI) is a lysosomal storage disorder caused by deficient activity of Arylsulphatase B (ARSB). While there is no cure for MPS VI, various treatment options are available to manage the symptoms and slow down disease progression.

Enzyme Replacement Therapy (ERT)

ERT is a widely used treatment for MPS VI. It involves administering enzymes that can break down the accumulated mucopolysaccharides in the body. Galsulfase (Naglazyme) is an FDA-approved ERT for patients with MPS VI, and it has been shown to improve walking ability and reduce symptoms [5][9].

Symptom-Based Treatment

Symptom-based treatment addresses individual complications of MPS VI as they arise. This may include antibiotics and other medications to manage infections, pain management, and respiratory support [7]. A multidisciplinary team approach is essential for optimal management of MPS VI.

Other Treatment Options

While ERT is the primary treatment for MPS VI, other options such as pentosan polysulfate and gene therapy are being explored. These treatments may be used in combination with ERT or as an alternative [6].

Importance of Early Diagnosis and Multidisciplinary Care

Early diagnosis and a multidisciplinary team approach are crucial for effective management of MPS VI. This includes a team of healthcare professionals, including doctors, nurses, physical therapists, and social workers.

References:

• [1] Drugs.com Mobile App provides information on medications used to treat MPS VI.
• [2] Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disorder caused by deficient activity of Arylsulphatase B (ARSB).
• [3] Enzyme replacement therapy (ERT) is approved for patients with MPS I, II, IV, VI, and VII.
• [4] Galsulfase (Naglazyme) has been shown to improve walking ability in patients with MPS VI.
• [5] FDA approval of galsulfase (Naglazyme) for the treatment of MPS VI.
• [6] Additional treatment options such as pentosan polysulfate and gene therapy are being explored.
• [7] Symptom-based treatment addresses individual complications of MPS VI.
• [8] Multidisciplinary team approach is essential for optimal management of MPS VI.

Differential Diagnosis of Mucopolysaccharidosis VI (MPS VI)

Mucopolysaccharidosis VI (MPS VI), also known as Maroteaux-Lamy syndrome, is a lysosomal storage disease caused by the deficiency of arylsulfatase B enzyme. The differential diagnosis of MPS VI involves distinguishing it from other forms of mucopolysaccharidoses and related disorders.

Key Points to Consider:

• MPS I vs. MPS VI: MPS I can be differentiated from MPS VI by the excretion of both heparan sulfate and dermatan sulfate in urine, whereas MPS VI is characterized by near 100% dermatan sulfate excretion [6].
• Multiple Sulfatase Deficiency (MSD): MSD should also be considered in the differential diagnosis, as it can present with similar clinical features to MPS VI [7].
• Other Forms of MPS: The differential diagnosis should include other forms of mucopolysaccharidoses, such as MPS I, II, IV A, and VII, as well as sialidosis and mucolipidosis [7].

Clinical Features:

• Progressive Multisystem Involvement: MPS VI is characterized by progressive multisystem involvement, including skeletal, cardiac, and respiratory systems [5].
• Dermatan Sulfate Accumulation: The accumulation of dermatan sulfate in lysosomes leads to cellular dysfunction and clinical abnormalities [1].

Diagnostic Approaches:

• Enzyme Replacement Therapy (ERT): ERT for MPS VI has been shown to be effective in reducing the accumulation of dermatan sulfate and improving clinical outcomes [10].
• Mass Spectrometry-Based Analysis: Mass spectrometry-based analysis of urine free glycosaminoglycans can aid in the differential diagnosis of MPS VI and other forms of mucopolysaccharidoses [12].

References:

[1] Cimaz et al. (2017) - Differential diagnosis algorithm for MPS.

[5] Harmatz P, Shediac R. (2017) - Mucopolysaccharidosis VI: Pathophysiology, diagnosis and treatment.

[6] Thumler A, Miebach E, Lampe C, et al. (2017) - Clinical characteristics of adults with slowly progressing mucopolysaccharidosis VI.

[7] Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI; MPS VI).

[10] Enzyme replacement therapy for mucopolysaccharidosis VI from 8 weeks of age—a sibling control study.

[12] Mucopolysaccharidoses Differential Diagnosis by Mass Spectrometry-Based Analysis of Urine Free Glycosaminoglycans—A Diagnostic Prediction Model.