Morquio’s disease is a very rare metabolic disorder caused by an enzyme defect. In this disorder, the breakdown of glycosaminoglycans is impaired, causing damage to the affected tissue.
What is Morquio’s disease?
Morquio’s disease was first described by pediatrician Luis Morquio in 1929. It is a congenital metabolic disorder caused by a defective protein. Depending on the defect, a distinction can be made between Morquio disease type A and Morquio disease type B, respectively.
Causes
Morquio disease is a heritable disorder, with autosomal recessive inheritance. If the mother and father carry a defective gene, this gene can be transmitted to the child. As a result, the corresponding enzyme is not produced in the body and the child subsequently develops Morquio’s disease. Depending on the enzyme defect, a distinction is made between Morquio disease type A and Morquio disease type B, respectively. In Morquio’s disease type A, there is a defect in a 6-sulfatase. As a result, endogenous glycosaminoglycans cannot be completely degraded and cleavage products are produced which are stored in lysosomes. In some cases, there is also increased excretion of these intermediates, such as keratan sulfate in Morquio’s disease type A or chondroitin-6-sulfate in Morquio’s disease type B.
In addition, the cleavage products are stored in the liver, spleen, connective tissue, eye and skeletal system, where they cause functional disorders. In this case, they are stored only in connective tissue cells and not in the central nervous system, so patients have normal intelligence.
Symptoms, complaints, and signs
The severity of Morquio disease varies, and sometimes the disease is not detected until adulthood due to a lack of symptoms. Typical symptoms include short stature with a very short neck, knock knees, and corneal opacities. The intelligence of the affected person is not diminished, liver and spleen are also not enlarged. Morbus Morquio patients rarely reach a height of over 120 centimeters. The short stature is due to shortened long bones, which is often not noticed until the fourth year of life. In addition, the affected persons have a keel chest, their joints are overmobile and the face resembles gargoyles, so that these changes are also called gargoylism. The chin is prominent and enlarged, the head is relatively large and the cheeks are quite pronounced. Also very noticeable are the bone changes that can be seen in the spine. The vertebrae between the lumbar and thoracic spine often have the shape of a wedge, the vertebral bodies are relatively flat and the so-called deus axis (odontoid process of the second cervical vertebra) is not appropriately fixed, which can lead to spinal stenosis or even paraplegia. The spinal cord may also be damaged by the instability and neurological deficits such as sensory disturbances or paresis may occur. Furthermore, the teeth often have defects in the enamel, and very often there are also hernias and umbilical hernias, requiring surgery.
Diagnosis and course of the disease
Morquio’s disease can be diagnosed by demonstrating a high excretion of chondroitin sulfate or keratan sulfate, respectively. In addition, radiographic examination of the ankles, wrists, or spine can be informative, as these usually show marked skeletal changes. Furthermore, it is possible to determine the activity of the defective enzyme in fibroblasts or leukocytes. If a gene alteration exists within the family, then an examination can be performed during pregnancy to determine whether a disease may be present in the unborn child.
Complications
Due to Morquio’s disease, patients suffer from various malformations on the body. In most cases, so-called knock knees occur, which can lead to restricted movement and thus to severe limitations in everyday life. Likewise, a clouding of the cornea occurs and the patients suffer from a very short neck. However, the intelligence of the affected person is not affected by Morquio’s disease. Furthermore, short stature also occurs. Especially for children this can mean bullying or depression, because they feel uncomfortable with their stature.It is also not uncommon for the head to be unusually large, possibly resulting in inferiority complexes or decreased self-esteem. Furthermore, Morquio’s disease can lead to paralysis or disturbances in sensitivity over the entire body, significantly reducing the quality of life. Various defects also occur in the teeth, which can make everyday life more difficult. The treatment of Morquio’s disease is symptomatic and aims at reducing the symptoms. In this way, infections of the respiratory tract can be avoided. Likewise, those affected are dependent on taking medication and on physiotherapy. No particular complications occur during the treatment itself.
When should one go to the doctor?
As an extremely rare congenital metabolic disorder, the enzyme defect called “Morquio’s disease” is not a common occurrence. In addition, the associated symptoms sometimes don’t show up until adulthood. This often delays a visit to the doctor. However, the fact that the massiveness of the symptoms does not lead to complaints in some people with Morquio’s disease is unusual. In most cases, this disease is unmistakable in view of the typical symptoms that appear, such as short stature in the range of 120 centimeters in height, strikingly short neck or X-legs. The shape of the face also indicates accompanying gargoylism at an early stage. A visit to the doctor also reveals massive skeletal changes. The skeletal malformations associated with Morquio’s disease require treatment. There are also increased risks of anesthesia. This complicates surgical procedures designed to correct painful deformities or restricted movement. Apart from symptomatic treatment, physicians have not been able to do much for those affected. Some clinics are already testing new enzyme replacement therapies for patients with Morquio’s disease. Since the accompanying symptoms of this disease often lead to inferiority complexes or bullying experiences, psychotherapeutic care should also be considered. Regular visits to the doctor or physiotherapeutic measures are unavoidable in Morquio’s disease. Visual and hearing impairments as well as immunological problems must be treated. Only with appropriate medical treatment, life expectancy can be estimated at 50 years.
Treatment and therapy
Treatment of Morquio’s disease is mainly symptomatic (surgery, prostheses, vertebral fusion to stabilize the neck), and enzyme replacement therapy is also currently being tested. Provision of assistive devices and physiotherapy treatment also play an essential role. Many children who have Morquio’s disease often also have hearing problems, so a hearing aid may seem appropriate in some cases. Acute bacterial infections are very often treated with antibiotics. To prevent respiratory infections, removal of tonsils and adenoids is also recommended. Furthermore, thorough dental care is important, as the enamel of the teeth is not very resistant. The clouding of the cornea usually does not affect the ability to see, but those affected are often very sensitive to light, and tinted eyeglass lenses can help here. It is also important to have an ultrasound examination of the heart at regular intervals, as storage material is also deposited in the heart muscle. If there are problems in the skeletal system, physiotherapy is advisable, as it can relieve pain and also delay joint stiffness. In addition, the strength of the joints can be supported with special splints. Comprehensive neurological examinations are also important in order to detect any complications in the cervical spine in good time. Furthermore, in Morbus Morquio patients, anesthesia should only be performed by a very experienced physician, as certain precautions are required. The prognosis depends on the severity of the disease and the quality of treatment. With appropriate treatment, affected individuals usually reach an age of more than 50 years.
Outlook and prognosis
Morquio’s disease is incurable. The prognosis is based on the symptom pattern and the time of initiation of therapy. Affected children must be provided with the necessary assistive devices at an early stage to prevent further damage and improve quality of life. Affected children can, for example, use tinted spectacle lenses to protect their light-sensitive eyes from the sun’s rays.With comprehensive treatment, a life expectancy of over 50 years is possible. The prospect of a symptom-free life exists if the symptoms are treated comprehensively and no serious health complications occur, such as respiratory infections. Regular ultrasound examinations of the heart can additionally improve the prognosis. Affected individuals also require therapeutic care to help them cope with the consequences of the disease. The sooner therapy is initiated, the better the prospects. Therefore, a doctor should be consulted at the first suspicion. The extreme rarity of the disease can have a negative impact on the prognosis, as the condition may not be diagnosed until late. Examinations by appropriate specialists in genetic alterations are necessary to obtain a diagnosis at an early stage and to initiate treatment of Morquio’s disease.
Prevention
Because Morquio disease is a hereditary disease, it cannot be prevented. However, in the case of an existing disease, it is possible to ensure treatment success by timely therapy. If there are already cases of Morquio’s disease in the family, human genetic counseling can be sought if there is an existing desire to have children, so that the risk can be better assessed.
Follow-up
Morquio disease is a hereditary disease based on an enzyme defect. The disease is primarily treated symptomatically, as enzyme replacement therapy is currently still in the experimental stage. Therapy is therefore mostly limited to aids designed to make everyday life more bearable for the patient. Prostheses must be precisely fitted and replaced if necessary. Dark-tinted glasses and sunglasses protect the sensitive eyes from strong light, hearing aids improve the often increasing hearing loss. Very thorough dental care is necessary, since in many cases of Morquio’s disease tooth enamel is not sufficiently formed. The extremely rare disease is often accompanied by social ostracism. Especially in childhood, patients suffer from teasing and bullying because of their deformities such as short stature, X-legs and unnatural head size. Here, the empathy of parents and other contacts is especially needed. Psychotherapeutic help is therefore recommended for both the affected person and the relatives. Relaxation techniques such as yoga can also contribute to psychological stabilization and give new strength. Since Morquio’s disease is very rare, self-help groups are seldom found. More information about the disease is available from the Society for Mucopolysaccharidoses.
What you can do yourself
If the child has been born with Morquio’s disease, the parents and other relatives are initially challenged. Because enzyme replacement therapy is still in the experimental stage, Morquio disease is treated symptomatically. Here, a high degree of adherence to therapy is important. Prostheses, for example, must be precisely adjusted and replaced and renewed as needed. This also applies to other aids such as dark-tinted glasses and sunglasses to protect the light-sensitive eyes, as well as hearing aids. Since Morquio’s disease is often associated with insufficiently formed tooth enamel, regular, thorough dental care is important. Morquio’s disease is usually associated with short stature, knock knees and other deformities, especially of the head, which is why the affected children are often teased or even bullied. This gnaws at their self-confidence and makes psychotherapeutic treatment advisable. The relatives should also seek psychotherapeutic support in order to be able to meet the demands that a child with Morquio’s disease places on them. Relaxation techniques such as yoga or Reiki bring balance and also give strength. Because the disease is extremely rare, there is no corresponding self-help group in this country that those affected and their relatives could join. However, because Morquio’s disease belongs to the mucopolysaccharidoses, the Society for Mucopolysaccharidoses e.V. also provides information about Morquio’s disease (www.mps-ev.de/mps/mukopolysaccharidosen).
