Maroteaux-Lamy Syndrome

Maroteaux-Lamy Syndrome

The Maroteaux-Lamy syndrome is one of the mucopolysaccharidoses, which include various lysosomal storage diseases. The syndrome is due to a genetic mutation that results in insufficient enzyme activity and leads to dermatin sulfate deposits. The therapy consists mainly of enzyme replacement therapies.

What is Maroteaux-Lamy Syndrome?

The mucopolysaccharidoses are an independent group of diseases that include lysosomal storage diseases. Lysosomal storage diseases are around. All of these are genetically determined metabolic diseases that are caused by malfunctioning of the lysosome. One of these disorders is what is known as Maroteaux-Lamy syndrome. The congenital metabolic disorder leads to a storage of dermatin sulfates. For ncaa – national collegiate athletic association, please visit ablogtophone.com.

The terms mucopolysaccharidosis type VI, arylsulfatase B deficiency, ARSB deficiency and ASB deficiency as well as N-acetylgalactosamine-4-sulfatase deficiency are regarded as synonyms. The disease was first described in 1963. The Parisian human geneticists and pediatricians P. Maroteaux and M. Lamy are considered the first to describe it.

The prevalence of the disease is between one and nine affected people in 100,000. Familial accumulation has been observed in the cases documented so far. The inheritance of the syndrome is autosomal recessive. A genetic mutation is believed to be the cause of the disease.

Causes

The Maroteaux-Lamy syndrome goes back to a mostly hereditary mutation. The causative mutations have now been localized to the ARSB gene. Mutations at the gene locus 5q13 to 5q14.1 are said to be able to cause the complex of symptoms. The genes located there code for a specific protein within the DNA.

Mutation of the genes is thought to result in abnormal activity of mutant arylsulfatase B, also known as ASB or N-acetylgalactosamine-4-sulfatase. The activity of the substance is reduced as part of the mutation. Due to this reduction, there are disturbances in the breakdown of substances such as chondroitin sulfate and dermatan sulfate. Since the substances are no longer broken down to a sufficient extent due to the causal mutation, the body stores residues of the substances.

The typical symptoms of Maroteaux-Lamy syndrome are a result of this storage. It is not yet known whether, in addition to genetic factors, external influences also play a role in the development of the mutation. At least for new mutations, however, this can be assumed.

Symptoms, Ailments & Signs

Patients with Maroteaux-Lamy syndrome suffer from a complex of clinically characteristic criteria. One of the most important symptoms is a disproportionately short stature, which is characterized by a short torso. The disproportionality of the patients is associated with a coarsened face reminiscent of the symptoms of Hurler’s disease.

In most cases, the patient’s cornea is cloudy. In addition, hepatosplenomegaly, hernias, or contractures of the joints may be present. The heart valves of the patients thicken due to the deposits. Skeletal dysplasia resembling that seen in patients with dysostosis multiplex may also be present.

Both the clinical picture and the course of the syndrome are considered variable and individual. In addition to slow courses, fast courses were also documented. If the first symptoms manifest themselves immediately after birth, this phenomenon indicates a rather rapid course.

This applies above all to an increase in glycosaminoglycan in the urine, to severe dysostosis multiplex and manifest short stature. Patients with a slow progression usually show the first symptoms much later. The GAG ​​elevation is much lower and the dysostosis multiplex is much milder.

Diagnosis & disease progression

Maroteaux-Lamy syndrome does not necessarily have to manifest itself immediately after birth and in many cases is only diagnosed later, when the first symptoms appear. The diagnosis is based on the clinically typical criteria of the disease and is thus primarily based on a significantly reduced ASB activity, which can be reproduced on cultured fibroblasts and leukocytes.

On the other hand, there is normal activity in relation to other sulfatases. In the urine, the doctor also provides evidence of increased excretion of dermatan sulfate as part of the diagnostics. In terms of differential diagnosis, Maroteaux-Lamy syndrome must be differentiated from multiple sulfatase deficiency and other forms of mucopolysaccharidosis. Sialidosis and mucolipidosis are diseases relevant to the differential diagnosis. The prognosis of the patients varies from case to case and mainly depends on the age of onset and the severity of the first symptoms.

Complications

First and foremost, the Maroteaux-Lamy syndrome leads to short stature in the patient. Children in particular at a young age can suffer from bullying and teasing and thus develop psychological problems or depression. As a rule, the further growth of the patient is not proportional and various complaints and malformations occur, which also appear on the face.

Furthermore, the heart valves are also damaged and out of place due to the Maroteaux-Lamy syndrome, so that there are complaints or restrictions on the heart. In some cases, this also reduces the patient’s life expectancy, which can lead to cardiac death. A causal treatment of this syndrome is not possible. For this reason, treatment is primarily aimed at limiting and combating the symptoms so that the person concerned can lead an ordinary life.

Psychological treatment may also be necessary. There are no particular complications, although not all symptoms can be completely curbed. As a rule, life expectancy is not reduced by Maroteaux-Lamy syndrome if there are no heart problems.

When should you go to the doctor?

If disorders or changes in the physical development process become apparent in a growing child, a doctor must be consulted. If the child is significantly short of stature or has a malformation of the skeletal system, it needs medical help. If there are abnormalities or peculiarities of the body shape in a direct comparison to children of the same age, a doctor should be consulted to clarify the symptoms. Disorders of the movement sequences or the general motor function must be presented to a doctor. A doctor is also needed if the cornea is cloudy or if your vision is reduced. Irregularities in the heart rhythm indicate a health impairment that must be examined in various medical tests.

In most cases, the first signs of the disease can be recognized immediately after birth due to the changes in the skeletal system. Since the infants are extensively examined by the doctor present after delivery, there is no need for action on the part of the parents. If symptoms such as vomiting or pain occur in the first few weeks or months of life, a doctor must be consulted. If the child is constantly screaming and crying, this is a sign of an irregularity that needs to be investigated. In the event of shortness of breath or an acute health-threatening condition, an emergency service must be alerted. Until it arrives, first aid measures must be taken to ensure the child’s survival.

Treatment & Therapy

A causal therapy is not available for patients with Maroteaux-Lamy syndrome in the narrower sense, since the altered enzyme activity in those affected is due to a genetic mutation that could only be corrected by gene therapy. However, with enzyme replacement therapy in the broadest sense, a type of therapy is available that addresses the symptoms of the disease at their source.

In enzyme replacement therapy, patients receive galsulfase in the sense of naglazymes. This enzyme replacement results in better breakdown of the relevant substances and thus delays the progression of the disease. However, the symptoms that have occurred so far cannot be completely reversed. Heart valve thickening may be treated symptomatically and may, under certain circumstances, require heart valve replacement surgery.

Acute hernias are treated using taxis. The goal is a reduction that gives the doctor time to find an operative solution. Severe corneal opacity resulting in blindness can sometimes be reversed with a corneal transplant. Symptoms such as short stature cannot ultimately be reversed, but often only occur in a mild form if an enzyme replacement drug is given early.

Outlook & Forecast

This rare disease occurs with a wide range of manifestations and forms. Thanks to the individual course and the different characteristics of Maroteaux-Lamy syndrome or mucopolysaccharidosis type 6, it is usually difficult to make a reliable prognosis for a specific patient.

In general, the prognosis is worse if the first symptoms of Maroteaux-Lamy syndrome appear shortly after birth. This usually indicates a faster progression of the disease.

Consequently, it can be said that the age of those affected also allows a conclusion to be drawn about the prognosis to be expected, as does the time at which the first symptoms of Maroteaux-Lamy syndrome appeared. In addition, the prospects for the patient also depend on the quality of the treatment. The point at which enzyme replacement therapy is initiated is often critical.

Enzyme replacement therapy can break down substances such as chondroitin sulfate and dermatan sulfate. It thus slows down the course of the disease. The problem, however, is that damage that has already occurred in the organism is usually not reversible. This reduces the quality of life, but can also result in the affected person dying earlier. The course of Maroteaux-Lamy syndrome can be rapid if it occurs early. However, the patient may also respond well to the medication administered. In this case, the Maroteaux-Lamy syndrome will progress correspondingly slowly.

Prevention

So far, no external factors are known for the development of Maroteaux-Lamy syndrome. The only preventive measure currently is genetic counseling when planning a family.

Aftercare

Since the treatment of Maroteaux-Lamy syndrome is complex and long-term, there is no need for classic follow-up care. Rather, those affected should focus on dealing with the disease safely and building a positive attitude despite the adversities. Relaxation exercises and meditation can also help to calm and focus the mind. Since short stature is associated with a reduction in aesthetics, any inferiority complexes and low self-esteem that may arise should be discussed with a therapist. This can help to better accept the disease and improve the quality of life in the long term.

You can do that yourself

Opportunities for self-help are not available to those affected by Maroteaux-Lamy syndrome. The disease can only be treated symptomatically, a causal therapy cannot take place here.

In order to alleviate the symptoms of the disease, those affected have to take enzymes and various medications. Care should be taken to ensure that it is taken regularly and as prescribed. In severe cases, however, surgical interventions on the heart are necessary. In order not to unnecessarily burden the heart, unnecessary efforts should be avoided. This applies above all to sudden or abrupt loads.

If the patient or the parents wish to have another child, genetic counseling can be useful in order to prevent the recurrence of Maroteaux-Lamy syndrome. Talking to those closest to you or friends can often alleviate mental health problems or depression. Contact with other patients with Maroteaux-Lamy syndrome also often has a very positive effect on the disease and can contribute to an exchange of information that may improve the quality of life of those affected. However, a complete cure of the syndrome cannot be achieved.

Maroteaux-Lamy Syndrome