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Mucopolysaccharidosis type VI (Maroteaux-Lamy)
MPS VI is a progressive genetic condition where specific enzymes are missing or not working correctly. This leads to a build-up of complex sugar molecules in cells, causing damage to various organs and tissues throughout the body. It can affect children and adults.
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Overview
Mucopolysaccharidosis type VI (MPS VI), known as Maroteaux-Lamy syndrome, is a rare inherited metabolic disorder. It belongs to a group of conditions called lysosomal storage disorders. In MPS VI, the body cannot properly break down complex sugar molecules called glycosaminoglycans (GAGs), specifically dermatan sulphate. This inability causes GAGs to accumulate within the lysosomes of cells, leading to progressive cellular damage and a range of health problems [PMID:31720689].
The severity and rate of progression of MPS VI can vary significantly between individuals. While some people experience severe symptoms early in life, others might have a more slowly progressing form of the condition. MPS VI is estimated to affect around 1 in 250,000 newborns.
Symptoms & clinical features
The symptoms of MPS VI typically appear in early childhood and tend to progress over time, though the rate of progression varies. Common features include skeletal abnormalities such as short stature, joint stiffness, and changes in bone shape, which can affect mobility. Individuals may also develop a characteristic facial appearance, often described as 'coarse', and an enlarged liver and spleen (hepatosplenomegaly) [PMID:28775438].
Other potential symptoms can involve the heart, with thickening of heart valves being a frequent finding. Respiratory issues may arise due to airway narrowing or skeletal changes in the rib cage. Eye problems, such as clouding of the cornea, are also common. Neurological involvement is typically less pronounced in MPS VI compared to some other MPS types; however, spinal cord compression can occur due to skeletal changes, which may require medical attention [PMID:28775438].
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Affected organs
MPS VI can affect many different organ systems throughout the body due to the widespread accumulation of GAGs. The skeletal system is notably impacted, leading to abnormal bone development, joint stiffness, and potential spinal cord compression. The liver and spleen often become enlarged, and the heart can be affected by the thickening of its valves, particularly the mitral and aortic valves.
Eyes are commonly affected, with corneal clouding reducing vision. The respiratory system may be compromised due to changes in the airways and rib cage, potentially leading to breathing difficulties. While the brain itself is generally not directly affected, spinal cord compression can lead to neurological symptoms. Hearing impairment can also occur.
Risks & severity
The severity of MPS VI exists on a spectrum, from rapidly progressing forms with early onset and significant health challenges, to more attenuated (milder) forms where symptoms develop later and progress more slowly. The rapidly progressive form typically manifests in early childhood with severe skeletal deformities, cardiac involvement, and respiratory issues, often leading to a reduced life expectancy if untreated.
Individuals with the attenuated form may experience milder symptoms that develop later, potentially into adolescence or adulthood, with a slower rate of progression. However, even attenuated forms can lead to serious complications if not managed appropriately. Complications can include severe skeletal issues, heart failure, and respiratory compromise. Early diagnosis and intervention can help manage symptoms and improve outcomes, though the condition remains progressive.
Genetic causes
Mucopolysaccharidosis type VI is caused by pathogenic variants in the *ARSB* gene. This gene provides instructions for making an enzyme called arylsulphatase B, also known as N-acetylgalactosamine-4-sulphatase. This enzyme is crucial for breaking down specific glycosaminoglycans (GAGs), particularly dermatan sulphate, within the cell's lysosomes [PMID:28775438].
When there are changes in the *ARSB* gene, the resulting enzyme may be absent, deficient, or non-functional. This impairment prevents the effective breakdown of dermatan sulphate, causing it to accumulate in the lysosomes of various cells and tissues throughout the body. The progressive build-up of these GAGs disrupts normal cellular function, leading to the diverse range of symptoms seen in MPS VI.
- ARSB arylsulfatase BThe ARSB gene encodes the enzyme arylsulfatase B, which plays a vital role in the breakdown of complex sugar molecules within cells.
Inheritance pattern
MPS VI is inherited in an autosomal recessive pattern. This means that an individual must inherit two altered copies of the *ARSB* gene, one from each parent, to develop the condition. If a person inherits only one altered copy and one typical copy of the gene, they are considered a 'carrier' and generally do not show symptoms of MPS VI themselves.
When two carriers have children, there is a 25% chance with each pregnancy that their child will inherit two altered gene copies and therefore develop MPS VI. There is a 50% chance the child will be a carrier, and a 25% chance the child will inherit two typical copies and not be a carrier. Family members of someone with MPS VI may consider genetic counselling to understand their own carrier status and reproductive risks.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosis of MPS VI typically begins with a clinical suspicion based on the characteristic symptoms. Initial screening tests may involve measuring GAG levels in urine, which are usually elevated in individuals with MPS VI. However, these tests can sometimes produce false negatives, particularly in attenuated forms.
A definitive diagnosis of MPS VI is confirmed through genetic testing, which looks for pathogenic variants in the *ARSB* gene. Enzyme assays, which measure the activity of the arylsulphatase B enzyme in blood or skin cells, can also confirm a diagnosis. In the UK, genetic testing for MPS VI is available through the NHS Genomic Medicine Service, often initiated following referral to a clinical genetics service or specialist paediatrician. This testing falls under specific R-codes for lysosomal storage disorders.
Management & lifestyle
Management of MPS VI focuses on alleviating symptoms, preventing complications, and improving quality of life. Enzyme replacement therapy (ERT) with galsulphase is a specific treatment for MPS VI, which helps to reduce the accumulation of GAGs, improve growth, joint mobility, and respiratory function, and reduce liver and spleen size [PMID:31720689]. ERT does not typically cross the blood-brain barrier effectively, so it has limited impact on central nervous system involvement.
Additional supportive care is often required, including regular monitoring of cardiac, respiratory, and skeletal systems. Orthopaedic interventions may be necessary to manage skeletal deformities or spinal cord compression. Physical therapy, occupational therapy, and speech therapy can help maintain function and address specific challenges. Regular follow-up with a multidisciplinary team, including specialists in genetics, paediatrics, cardiology, orthopaedics, and ophthalmology, is crucial for comprehensive care within the NHS framework.
UK care pathway
In the UK, individuals suspected of having MPS VI typically enter the NHS Genomic Medicine Service pathway. This often starts with a referral from a GP or specialist paediatrician to a clinical genetics service. Genetic counsellors play a key role, providing information about the condition, inheritance patterns, and supporting families through the diagnostic process. Diagnostic testing for MPS VI is covered by specific NHS R-codes under the rare and inherited disease categories.
Following diagnosis, care is managed by a multidisciplinary team, usually coordinated through specialist centres. This ensures access to enzyme replacement therapy, if appropriate, and ongoing surveillance and supportive care, aligning with national guidelines and best practices.
Frequently asked questions
What is the life expectancy for someone with MPS VI?
Life expectancy for individuals with MPS VI varies widely depending on the severity of the condition and access to treatment. With current treatments like enzyme replacement therapy, many individuals, particularly those with attenuated forms, can live into adulthood, often into their 40s or 50s and beyond, though the disease remains progressive.
Is there a cure for MPS VI?
Currently, there is no cure for MPS VI. However, treatments like enzyme replacement therapy (ERT) are available to help manage symptoms, slow disease progression, and improve quality of life. Research continues into new therapeutic approaches, including gene therapy.
How does MPS VI affect intellectual development?
Unlike some other types of mucopolysaccharidoses, MPS VI typically does not directly affect intellectual development. Individuals with MPS VI generally have normal intelligence. However, secondary issues like spinal cord compression or hearing loss can indirectly impact learning and communication.
Can MPS VI be detected before birth?
Yes, prenatal diagnosis for MPS VI is possible if the specific genetic changes in the parents are known. This can be done through chorionic villus sampling or amniocentesis. This option is typically discussed with families who already have a child with MPS VI or who are known carriers.
What kind of specialist care will someone with MPS VI need?
Individuals with MPS VI generally require care from a multidisciplinary team of specialists. This team may include geneticists, paediatricians, cardiologists, orthopaedic surgeons, ophthalmologists, ear, nose, and throat (ENT) specialists, anaesthetists, and physical therapists to manage the various aspects of the condition.