Maroteaux-Lamy disease is a “mucopolysaccharidoses”. This fancy term simply represents any disorder in which patients are unable to adequately metabolize long chains of repeating sugar units.
Another term for mucopolysaccharide is glycosaminoglycan, or “GAG”. GAGs are composed of long, repeating, un-branched sugar chains. Each repeating unit has a six carbon sugar (ie: the general term for a simple six carbon sugar is a “hexose”; glucose, mannose, galactose, etc. are specific examples) attached to another six carbon sugar that has a nitrogen group sticking off of it; the general name for a six carbon sugar with an attached nitrogen group is a “hexosamine”.
These two-sugar units, a hexose plus hexosamine, connect to one another over and over again to form a very long chain called a glycosaminoglycan.
GAGs and mucopolysaccharides are important in the human body because they make up a significant proportion of connective tissue. Connective tissues provide support and structure to all of the various organ systems. As such, the body is constantly forming, breaking down, and re-molding GAGs to provide the structural framework so that the rest of our cells can do their jobs appropriately.
So what do GAGs have to do with Maroteaux-Lamy disease? A specific GAG known as dermatan sulfate is not broken down appropriately in patient’s suffering from this condition.
The reason these individuals are unable to break down dermatan sulfate is because they have a genetic mutation in the enzyme arylsulfatase B. In a normal person, arylsulfatase B degrades excess and unwanted dermatan sulfate; however, when the enzyme is defective it causes dermatan sulfate to build up to abnormally high levels within cells.
This excess dermatan sulfate eventually “gunks” up various organ systems and results in the characteristic signs and symptoms associated with the disease.
It is important to realize that there are hundreds of genetic mutations that can cause Maroteaux-Lamy disease; and not all mutations are created equal! Therefore, there is a wide spectrum of signs and symptoms that may occur quickly or slowly depending on which particular mutation the patient has.
Most patients are short and have progressive changes in their facial features. Patients often develop early onset vision problems because their corneas become clouded by excess dermatan sulfate. Joint stiffness and skeletal abnormalities are also very common, as are heart and lung complications.
The lining of the brain and spinal cord can become excessively thick which can cause weakness secondary to spinal cord and nerve compression.
Patient’s also often have enlargement of the spleen – a condition called “splenomegaly”. It is not uncommon for patients to have various types of hernias.
Unlike patient’s suffering from some of the other mucopolysaccharidoses, people with Maroteaux-Lamy are of normal intelligence.
Overall, Maroteaux-Lamy disease is more appropriately a “syndrome”, or constellation of signs and symptoms. By themselves, each sign or symptom is not diagnostic of the disorder, but when present together can support the diagnosis.
Genetic testing for mutations of the arylsulfatase B gene are done once the syndrome is suspected on clinical grounds. Additionally, urine samples contain elevated amounts of dermatan sulfate.
Treatment consists of using a replacement enzyme known as Naglazyme® (aka: galsulfase). This enzyme performs the function of the deficient arylsulfatase B and helps in the degradation of dermatan sulfate.
Stem cell transplants can also provide the missing enzyme, but at significant risk. Unfortunately, few patients are candidates for stem cell transplant given difficulty with donor matching.
A very important component of treatment is monitoring for progression of symptoms. This will allow specialists to step in and perform palliative procedures that can prevent worsening disability. For example, corneal transplants can be done to restore vision loss.
Maroteaux-Lamy is one of the mucopolysaccharidoses. It is caused by a genetic deficiency in the enzyme arylsulfatase-B, which prevents the degradation of dermatan sulfate. It presents with a host of signs and symptoms, which may be rapidly or slowly progressive depending on the specific genetic mutation. Treatment is with enzyme replacement therapies and palliative care.
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