Maroteaux-Lamy syndrome is one of the mucopolysaccharidoses, which include various, lysosomal storage diseases. The syndrome results from a genetic mutation that results in insufficient enzyme activity and leads to dermatin sulfate storage. Therapy consists primarily of enzyme replacement therapies.
What is Maroteaux-Lamy syndrome?
The mucopolysaccharidoses are a distinct group of disorders that include lysosomal storage diseases. Lysosomal storage diseases come in round numbers. All of them are genetic metabolic diseases caused by malfunctions of the lysosome. One of these diseases is the so-called Maroteaux-Lamy syndrome. The inborn error of metabolism leads to a storage of dermatin sulfates. Synonyms are mucopolysaccharidosis type VI, arylsulfatase B deficiency, ARSB deficiency and ASB deficiency, and N-acetylgalactosamine-4-sulfatase deficiency. The disease was first described in 1963, and the Paris human geneticists and pediatricians P. Maroteaux and M. Lamy are considered the first describers. The prevalence of the disease is between one and nine affected persons per 100,000 people. Familial clustering has been observed in the cases documented to date. Inheritance of the syndrome is autosomal recessive. A genetic mutation is thought to be the cause of the disease.
Causes
Maroteaux-Lamy syndrome results from a mostly hereditary mutation. The causative mutations have now been localized to the ARSB gene. Thus, mutations at gene locus 5q13 to 5q14.1 are thought to cause the complex of symptoms. The genes located there code within the DNA for a specific protein. Mutation of the genes is thought to result in abnormal activity of the mutant arylsulfatase B, also known as ASB or N-acetylgalactosamine-4-sulfatase. Its activity is reduced as part of the mutation. Due to this reduction, there are disturbances in the degradation of substances such as chondroitin sulfate and dermatan sulfate. Since the substances are no longer broken down to a sufficient extent due to the causative mutation, the body stores residues of the substances. The typical symptoms of Maroteaux-Lamy syndrome are a consequence of this storage. It is not yet known whether external influences play a role in the development of the mutation in addition to genetic factors. However, at least for new mutations, it can be assumed.
Symptoms, complaints, and signs
Patients with Maroteaux-Lamy syndrome suffer from a complex of clinically characteristic criteria. Among the most important symptoms is a disproportionate short stature characterized by a short trunk. The disproportionality of the patients is associated with a coarsened face reminiscent of the symptoms of Hurler’s disease. In most cases, the patients’ corneas are opacified. In addition, hepatosplenomegaly, herniation, or contractures of the joints may be present. The patients’ heart valves progressively thicken due to the debris. Furthermore, dysplasia of the skeleton may be present, resembling that of patients with dysostosis multiplex. Both the clinical picture and the course of the syndrome are considered variable and individual. In addition to slow courses, rapid courses have also been documented. If the first symptoms manifest immediately after birth, this phenomenon suggests a rather rapid course. This is especially true for an increase in gycosaminoglycan in the urine, for severe dysostosis multiplex and manifest short stature. Affected individuals with a slow course usually show first symptoms much later. The GAG elevation is much lower and the dysostosis multiplex much milder.
Diagnosis and course of the disease
Maroteaux-Lamy syndrome does not necessarily manifest immediately after birth and in many cases is 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 substantially decreased ASB activity, which can be traced on cultured fibroblasts and leukocytes. In contrast, normal activity is present with respect to other sulfatases. In the urine, the physician also provides evidence of increased excreted dermatan sulfate as part of the diagnosis.Differentially, Maroteaux-Lamy syndrome must be distinguished from multiple sulfatase deficiency and other forms of mucopolysaccharidosis. Sialidosis or mucolipidosis are also differential diseases. The prognosis of patients varies from case to case and depends mainly on the age of manifestation and the severity of the first symptoms.
Complications
Primarily, Maroteaux-Lamy syndrome results in short stature in the patient. In this process, children, especially at a young age, may suffer from bullying and teasing and develop psychological symptoms or depression as a result. As a rule, the further growth of the patient is also not proportional and various complaints and malformations occur, also in the face. Furthermore, Maroteaux-Lamy syndrome also damages and dislocates the heart valves, causing discomfort or limitations in the heart. In some cases, this also reduces the life expectancy of the patient, so that cardiac death may occur. There is no causal treatment for this syndrome. For this reason, treatment is mainly aimed at limiting and controlling the symptoms so that the affected person can lead an ordinary life. Psychological treatment may also be necessary. There are no particular complications, although not all symptoms can be completely limited. As a rule, life expectancy is also not reduced by Maroteaux-Lamy syndrome in the absence of cardiac symptoms.
When should you see a doctor?
If disorders or changes within the physical development process become apparent in a growing child, a physician must be consulted. If there is a significant short stature or malformation of the skeletal system, the child needs medical attention. If abnormalities or peculiarities of the body shape are visible in direct comparison to children of the same age, a doctor should be consulted to clarify the complaints. Disturbances in movement or general motor function should be presented to a physician. If there is clouding of the cornea or decreased vision, a doctor is also needed. Irregularities of the heart rhythm indicate a health impairment, which must be examined in various medical tests. In most cases, the first abnormalities of the disease can be detected immediately after birth due to the changes in the skeletal system. Since the infants are extensively examined by the attending physician after delivery, there is no need for action on the part of the parents. If complaints such as vomiting or pain occur during the first weeks or months of life, a doctor must be consulted. If the child cries and cries continuously, this is a sign of an irregularity that needs to be clarified. In the event of respiratory distress or an acute health-threatening condition, an ambulance should be alerted. Until they arrive, first aid measures should be administered to ensure the child’s survival.
Treatment and therapy
Causative therapy is not available for patients with Maroteaux-Lamy syndrome in the strict sense, because the altered enzyme activity of affected individuals is due to a genetic mutation that could be corrected exclusively by gene therapy. However, enzyme replacement therapy in the broadest sense is a type of therapy that addresses the symptoms of the disease at their source. In enzyme replacement therapy, patients receive galsulfase in the form of naglazymes. This enzyme replacement results in better degradation of the relevant substances and thus delays the course of the disease. However, the symptoms that have occurred so far cannot be completely reversed. Heart valve thickening may be treated symptomatically and may require surgical replacement of the heart valves under certain circumstances. Acute hernias are treated by cabs. The goal is reduction, which allows the physician time to find a surgical solution. Severe corneal opacities resulting in blindness may be reversed by a corneal graft. Symptoms such as short stature ultimately cannot be reversed, but often occur only in a mild form with early care with an enzyme replacement medication.
Outlook and prognosis
This rare condition occurs with a wide range of manifestations and courses.Thanks to the individual course and varying expression of Maroteaux-Lamy syndrome or mucopolysaccharidosis type 6, it is usually difficult to give a reliable prognosis for a particular patient. In general, the prognosis is worse when the first symptoms of Maroteaux-Lamy syndrome appear shortly after birth. This usually indicates a more rapid progression of the disease. Consequently, it can be said that the age of the affected person is as much a conclusion about the expected prognosis as the time when the first symptoms of Maroteaux-Lamy syndrome appeared. In addition, the patient’s outlook also depends on the quality of treatment. The time at which enzyme replacement therapy was initiated is often critical. Enzyme replacement therapy can break down substances such as chondroitin sulfate and dermatan sulfate. It thus slows the progression of the disease. However, it is problematic that damage that has already occurred in the organism is usually not reversible. This reduces the quality of life, but can also result in an earlier death of the affected person. The course of Maroteaux-Lamy syndrome can be rapid if it occurs early. However, the patient may also respond well to the medications administered. In this case, the course of Maroteaux-Lamy syndrome will be correspondingly slow.
Prevention
To date, there are no known external factors for the development of Maroteaux-Lamy syndrome. Currently, the only preventive measure is genetic counseling during family planning.
Follow-up
Because treatment of Maroteaux-Lamy syndrome is complex and ongoing, traditional follow-up care is not required. Rather, affected individuals should focus on safely managing the condition and building a positive attitude despite adversity. To this end, relaxation exercises and meditation can help calm and focus the mind. Since short stature is associated with a reduction in aesthetics, any inferiority complexes and low self-esteem that arise should be discussed with a therapist, if necessary. The latter can help to better accept the condition and improve the quality of life in the long term.
What you can do yourself
Self-help options are not available to the person affected by Maroteaux-Lamy syndrome. The disease can only be treated symptomatically; causal therapy cannot be provided in this case. In order to alleviate the symptoms of the disease, those affected are dependent on taking enzymes and various medications. Regular and prescribed intake should be ensured. In severe cases, however, surgical interventions on the heart are necessary. To avoid unnecessary strain on the heart, unnecessary exertion should be avoided. This applies especially to sudden onset or abrupt stress. If the patient or parents wish to continue having children, genetic counseling may be useful in this context to prevent the recurrence of Maroteaux-Lamy syndrome. Often, conversations with the closest confidants or with friends can alleviate psychological discomfort or depression. Contact with other Maroteaux-Lamy syndrome patients also often has a very positive effect on the disease, and in the process can contribute to an exchange of information that may eventually improve the quality of life of the affected person. However, a complete cure for the syndrome cannot be achieved.
