Mucopolysaccharidosis: Causes, Symptoms & Treatment

Mucopolysaccharidosis is a collective term for lysosomal storage diseases based on the storage of glycosaminoglycans. All diseases develop similar symptoms and courses. The severity of the syndromes varies widely.

What is mucopolysaccharidosis?

There is no such thing as mucopolysaccharidosis as a single disease. The term mucopolysaccharidosis represents a collective term for a variety of storage disorders. These are based on storage disorders of glycosaminoglycans (GAG) in the lysosomes of cells. The storage is progressive because the degradation of the compounds does not work. All mucopolysaccharidoses are genetic. Each disease lacks a specific enzyme that catalyzes the degradation of the corresponding GAG. All mucopolysaccharidoses are very rare diseases and often have similar courses. If left untreated, the constantly increasing deposits destroy the cells. In the process, the organs are destroyed. The disease can start in infancy as well as in adulthood. Mucopolysaccharidosis can be caused by four different groups of glycosaminoglycans:

  • Heparan sulfate
  • Keratan sulfate
  • Chondroitin sulfate
  • Dermatan sulfate.

All glycosaminoglycans consist of a polysaccharide chain linked to a protein. Here, the carbohydrate portion accounts for 95 percent and the protein portion five percent of the molecular mass. Depending on which glycosaminoglycan and which enzyme is affected, a distinction can be made between six different main forms of mucopolysaccharidoses: These include Hurler / Scheie disease (MPS I), Hunter disease (MPS II), Sanfilippo disease (MPS III), Morquio disease (MPS IV), Maroteaux-Lamy disease (MPS VI), and Sly disease (MPS VII). In all types, there are severe and mild forms.

Causes

The cause of all mucopolysaccharidoses is increasing storage of glycosaminoglycans (GAGs) in the lysosomes of cells. The degradation of the corresponding biopolymers is disturbed. For each individual disorder, either a particular enzyme is missing or that enzyme is malfunctioning. There may also be several mutations for each enzyme. The inheritance of the corresponding mutation can be autosomal recessive, autosomal dominant or x-linked recessive. Since an enzymatic process usually involves multiple reaction steps, theoretically multiple enzymes can be mutated for the same glycosaminoglycan. However, the symptoms of the disorder would be the same or similar.

  • In MPS I, Hurler disease or Scheie disease, the enzyme alpha-l-iduronidase is defective.
  • MPS II represents Hunter’s syndrome with a defective iduronate-2-sulfatase.
  • Sanfilippo syndrome (MPS III) can be divided into several subtypes at once. In this disease, several enzymes may be affected.
  • Morquio’s disease (MPS IV) is caused by a defective β-galactosidase.
  • In Maroteaux-Lamy syndrome (MPS VI), it is the N-acetyl-galactosamine-4-sulfate sulfatase.
  • Sly’s disease (MPS VII) is caused by defective β-glucuronidase. When the corresponding glycosaminoglycans are stored in the lysosomes, they become increasingly larger.

In the process, the cells also increase in size because they need more and more space for undegraded GAGs. This is also noticeable in the enlargement of many organs. A typical symptom is the constant enlargement of the liver and spleen. If left untreated, storage diseases lead to death due to gradual destruction of the organs.

Symptoms, complaints and signs

Symptoms are similar in all diseases. There are severe and mild forms of progression. However, a mild course only means that the disease progresses more slowly. The final course is always the same. There are progressive deformities of the skeletal system, joint contractures, coarsening of facial features, and enlargement of the liver and spleen. Mental and motor abilities decrease in the short or long term. In the severe forms of the disorders, the clinical pictures are very similar. Early on, umbilical and inguinal hernias, heart problems, and respiratory infections develop. Over time, massive sleep apnea problems develop due to narrowing of the airways and enlargement of the palatine and pharyngeal tonsils.

Diagnosis and course of the disease

Mucopolysaccharidoses can be diagnosed by testing the urine for excreted glycosaminoglycans. In mucopolysaccharidosis, the levels are always elevated. Furthermore, the activity of the suspected defective enzyme can be determined in the leukocytes or fibroblasts. A specific excretion pattern of glycosaminoglycans directs suspicion to a corresponding enzyme, which is then examined.

Complications

As a result of mucopolysaccharidosis, affected individuals suffer from various skeletal deformities and complaints. Deformities occur that can significantly limit the patient’s daily life. As a rule, the joints are also affected by mucopolysaccharidosis, resulting in restrictions in the patient’s movement. Children in particular are affected and suffer from severely delayed development, so that various consequential damages can also occur in adulthood. It is not uncommon for mucopolysaccharidosis to lead to heart or respiratory problems. In the worst case, sudden cardiac death can lead to the death of the affected person. As a result of the respiratory problems, patients suffer from fatigue and exhaustion. The resilience of those affected also decreases enormously. It is not uncommon for breathing difficulties to lead to sleep problems at night and thus to depression. The patient’s quality of life is considerably reduced by mucopolysaccharidosis. Unfortunately, a causal treatment of this disease is not possible. Patients are therefore dependent on bone marrow donors to treat the symptoms. No particular complications occur in this process. However, in most cases, patients are dependent on lifelong therapy.

When should you go to the doctor?

Changes and abnormalities of the body structure indicate a health impairment. A visit to the doctor is necessary as soon as there are permanent visual peculiarities or the affected person has difficulty optimizing his posture at will. Swelling of the joints, changes in the facial features or enlargement of the chest should be examined intensively by a doctor so that a diagnosis can be made. If there are restrictions in the possibilities of movement, irregularities in the daily voluntary control as well as a decrease in physical as well as mental performance, a doctor is needed. In case of disturbances of heart rhythm, problems with respiratory activity as well as interruptions during night sleep, a doctor should be consulted. Swelling of the throat, a feeling of tightness in the pharynx, disturbances in the act of swallowing, as well as changes in phonation are considered worrisome. They must be assessed by a physician so that relief can be initiated. If the affected person suffers more infections, the concentration and attention capacity decreases or if there are repeated umbilical as well as inguinal hernias, a doctor must be informed about the observations. Sudden skin blemishes, yellowing of the complexion as well as inner restlessness should be examined and treated. A doctor is needed as soon as there is pain in the body, a decreased quality of life, as well as behavioral problems. If respiratory distress is imminent, an ambulance is needed. To prevent this acute condition, a physician should be consulted as early as possible.

Treatment and therapy

A causal therapy is not yet possible today. However, there are some approaches to a future gene therapy of these diseases in research projects. At present, tangible results in this field are unfortunately still pending. However, in Hurler’s disease, a clinical trial on gene therapy is to start in Barcelona. In some forms of mucopolysaccharidoses, bone marrow transplantation has proven successful in individual cases. This applies for example to Hunter’s disease, Hurler’s disease or Sanfilippo’s disease. Through this bone marrow transfer, the diseased stem cells are exchanged for healthy stem cells from a donor. This enables the organism to produce the missing enzyme again in sufficient quantities. Enzyme replacement therapy also pays off in many cases. However, this replacement therapy must be carried out for life. However, there are also cases in which no promising therapies are possible anymore. Here, however, the goal is to provide symptomatic treatments.

Outlook and prognosis

The further development in patients with mucopolysaccharidosis must be evaluated on an individual basis.This term is a collective term for various storage disorders. These are present to different degrees in each patient and are individually pronounced in their intensity. If medical care is not initiated, the internal organs are gradually destroyed in the course of the lifetime of all those affected. This results in a shortening of the average expected lifespan. If the diagnosis is made early, a personally optimized therapy can be worked out. This is linked to the patient’s health conditions and existing complaints. Long-term treatment is generally necessary to achieve a stable improvement in health. Surgical interventions may be necessary, each of which is associated with different risks and side effects. If the operation proceeds without further complications, an alleviation of the symptoms can normally be observed afterwards. Nevertheless, unwanted developments and setbacks may occur in the course of life. In individual cases, only a bone marrow transplant can then bring about an improvement in the general quality of life. Due to the overall circumstances, the patient experiences a strong emotional and mental burden. A normal daily routine is often not possible due to the complaints. Psychological sequelae may occur and lead to further deterioration of the situation.

Prevention

Because mucopolysaccharidoses are hereditary diseases, prevention is not possible. If the disease is present, timely therapy can ensure treatment success. Furthermore, constant monitoring of lung and heart function is necessary. If cases of mucopolysaccharidosis have already occurred in the family, the risk of the disease can be assessed by human genetic counseling if children are desired.

Follow-up

In most cases of mucopolysaccharidosis, the patient has few options for follow-up care, so the affected person should primarily see a physician early in the course of this disease. Only early detection and treatment of this disease can also prevent further complications, so a doctor should be contacted at the first signs and symptoms. In most cases, those affected rely on surgical interventions that can alleviate and limit the symptoms. However, since mucopolysaccharidosis is a genetic disease, it usually cannot be completely cured. Therefore, if a person wishes to have children, he or she should first consult a doctor to prevent the recurrence of this disease in the children. Often, the support of one’s family during treatment is also very important. This can also prevent depression and other psychological upsets. It is possible that mucopolysaccharidosis may result in a reduced life expectancy for the affected person, although the further course depends very much on the time of diagnosis.

What you can do yourself

The possibilities of self-help in mucopolysaccharidosis are limited to achieving a relief of the symptoms and thus an improvement in the quality of life. Self-help groups have been shown to be very helpful, as sharing with other parents reveals valuable tips as well as can often alleviate fears and concerns and provide a more positive outlook for the future. Accompanying the child to physiotherapy, occupational therapy, speech therapy and other forms of therapy, which can often also be intensified in the home environment, are from then on an integral part of life. In order to make life as easy as possible for yourself and the affected child, it is advisable to adapt the living environment to the needs of the disabled as early as possible. As the child grows older and weighs more, height-adjustable care beds prove to be a great physical relief for the caregivers. Epilepsy warning devices and other technical aids also enable the best possible safety at night and relieve parents at night so that they can sleep more relaxed. Keeping a symptom diary can help the doctor recognize new symptoms and possibly correct the treatment of existing symptoms, since drug therapy often does not have the desired effect, but the opposite one. Since the disease places great demands on the relatives, they must create small spaces of freedom for themselves in order to recharge their batteries.This may include cures, respite care or, later, a hospice leave.