In hypophosphatasia, a genetic enzyme defect prevents skeletal mineralization. Those affected suffer from skeletal deformities and are more likely to suffer fractions. Although no curative therapy is currently available, the disease may be curable in the future, for example with enzyme replacement therapy.
What is hypophosphatasia?
So far, no direct proof of the mutation is possible. An initial suspected diagnosis can only be made via the blood values. See AbbreviationFinder for abbreviations related to Hypophosphatasia.
Hypophosphatasia is a rare hereditary disease of bone metabolism. A phosphatase deficiency leads to numerous malformations of the skeleton in the context of this disease. The bones are not sufficiently mineralized in hypophosphatasia. The disease is, so to speak, a mineralization disorder in the narrower sense.
Hyperphosphatasia, in which over-mineralization occurs, must be distinguished from hypophosphatasia. This metabolic disorder is also genetic and can be inherited in an autosomal recessive manner. Hypophosphatasia is often confused with other bone diseases such as osteoporosis. An exact prevalence for the hereditary disease is not yet known.
A study found an approximate ratio of 1:100,000 for occurrence. The subgroups of the disease are the perinatal, infantile, adolescent and adult forms. In a broader sense, odontohypophosphatasia and pseudohypophosphatasia also belong to the group.
Genetic mutations cause hypophosphatasia. The mutation was localized to gene locus 1p34-36 of chromosome 1. The gene located there codes for the alkaline phosphatase enzyme. As a result of the mutation, only defective variants of this enzyme are formed, which show reduced activity. In healthy people, the enzyme forms phosphate from inorganic pyrophosphate by splitting it.
This phosphate is needed by osteoblasts for bone mineralization. If too little or only mutated alkaline phosphatase is present, the enzyme produces too little phosphate. The bones can therefore only be mineralized to a limited extent by the osteoblasts. There is too much inorganic pyrophosphate in the organism because it is only broken down to a limited extent. This over-concentration of inorganic pyrophosphate further inhibits bone formation and can precipitate the pyrophosphate calcium crystals in the organs.
Symptoms, Ailments & Signs
The severity of the disease determines the symptoms. The form of hypophosphatasia also has an impact on the symptoms that occur. As a rule of thumb, a disease that occurs early is considered to be more serious than the onset of the disease in the later decades of life. The infantile form in particular is therefore often lethal, since it leads not only to severe skeletal malformations but also to organic damage.
The adult form of the disease, on the other hand, is less severe. As a rule, hypophosphatasia causes bone curvature due to the lack of mineralization, which is associated with fractures. The tubular bones in particular are affected by these fractures. Tooth loss and high calcium levels are concomitant.
Rapid fatigue, muscle weakness, loss of appetite and pain can also occur. Inflammatory phenomena often accompany the fractures, as the inorganic pyrophosphate combines with calcium to form crystals and is deposited in the body. Hypophosphatasia is therefore often confused with osteoporosis or rheumatism.
Diagnosis & course of disease
Since hypophosphatasia is associated with a wide variety of symptoms and can also break out in any decade of life, diagnosing the disease is a challenge. So far, no direct proof of the mutation is possible. An initial suspected diagnosis can only be made via the blood values.
Both phosphoric ethanol and inorganic pyrophosphate and pyridoxal-5-phosphate are increased in those affected. Severe forms of the mineralization disorder can also be traced using an X-ray image, on which the skeleton can only be seen in outline. The prognosis is most unfavorable for infants with this condition. The lethality is high. A more favorable course is assumed for adults.
Hypophosphatasia usually leads to various malformations and deformations in the patient’s skeleton. Likewise, more common and simple fractures occur throughout the body. In most cases, the symptoms of hypophosphatasia do not appear until late adulthood. Children are mostly not affected by this disease.
Likewise, the malformation of the skeleton can also lead to damage to the organs, so that a transplant may be necessary for the patient to survive. It is not uncommon for a tooth to fall out, which can lead to problems with eating. The loss of teeth often leads to aesthetic complaints and thus to depression.
Furthermore, the patient’s resilience drops enormously and the affected person feels sick and tired. Severe pain and loss of appetite occur, which can lead to malnutrition. The everyday life of the patient is severely restricted by the hypophosphatasia and the quality of life is significantly reduced.
Treatment of hypophosphatasia can be carried out with the help of drugs and leads to a positive course of the disease. In many cases, therapy is also necessary. Life expectancy can be reduced if organ damage has occurred as a result of hypophosphatasia.
When should you go to the doctor?
If symptoms of hypophosphatasia are noticed, a doctor should be consulted . Medical advice is required if even light physical exertion leads to fatigue and muscle weakness. Other warning signs that need to be checked are loss of appetite and pain in the limbs. This is often accompanied by inflammation and increasing stiffness in the area of the joints. These signs are indicative of hypophosphatasia and require prompt evaluation and treatment if necessary. People who have had unusual muscle, joint, or bone pain for a long time and have no specific cause should also consult a doctor.
Since it is a genetic disease, any risk factors cannot be treated preventively. Only when the disease has been diagnosed can the course of the individual symptoms be slowed down. People who suspect a serious bone disease should speak to their family doctor. The doctor can make an initial diagnosis and then refer the patient to an orthopedist or bone disease specialist. Further treatment usually takes place in a specialist clinic.
Treatment & Therapy
Therapeutically, no curative treatment of hypophosphatasia is available. There is also no causal therapy in the current state of medicine. Therefore, treatment is usually symptomatic. Drug therapy is used to relieve symptoms. Both the administration of vitamin D and the administration of painkillers achieve symptomatic improvements in most cases.
Above all, the pain reduces the quality of life of those affected. Since symptomatic therapies are aimed in particular at improving the quality of life, pain relief is the focus of treatment. Patients with an increased concentration of prostaglandin E2 can be given a non-steroidal anti-inflammatory drug for five weeks for this purpose. In this way, physical activity can be increased again with less pain.
Physiotherapy, for example, can be useful as part of therapy to increase mobility. Any kind of physical activity has a positive effect on the course of the disease, since the targeted build-up of muscles can stabilize the musculoskeletal system. A change in diet is also recommended as part of the treatment. For example, a low-phosphate diet reduces elevated serum levels of phosphate and may reduce crystal formation.
If neurological symptoms occur that are caused by increased intracranial pressure, neurological intervention takes place. Medical research is now concerned with innovative concepts for the therapy of hypophosphatasia. In the future, curative treatments may be available with enzyme replacement therapy or xenograft transplantation.
Since hypophosphatasia is a hereditary disease based on a gene mutation, the disease cannot be prevented.
Following a treated hypophosphatasia, the patient is concerned, among other things, with improving mobility. Physiotherapy usually helps here. The improvement progresses quickly through physical exercise, because the musculature receives good stabilization. In the follow-up care, there is also an examination of the eating habits.
A low-phosphate diet can lower the concentration in the blood so that fewer crystals form. If neurological symptoms occur as a result of the illness, appropriate measures must be initiated in this area. For such a therapy, there is no general advice for aftercare.
This is related to the purely symptomatic treatment. Typically, patients need to take vitamin D for a long time. In addition, if the pain is severe, doctors prescribe helpful medication that relieves these symptoms. If those affected take the painkillers for a long time, however, damage to the stomach is to be expected.
Here it is important not to put too much strain on the body. A reduction in activity may be needed to relieve pain. Depending on the psychological problems that are often associated with the disease, individual psychotherapy may be advisable as part of the aftercare.
You can do that yourself
In the case of hypophosphatasia, the person affected usually has no options for self-help. The treatment of the disease is purely symptomatic, since a causal treatment is not possible. Patients are dependent on taking vitamin D. If those affected suffer from pain, painkillers must be taken. When taking painkillers, it should be noted that long-term use can damage the stomach.
Furthermore, physical activities should be limited if possible, as these are usually responsible for the pain. Therefore, the affected person is often restricted in his everyday life and should not do any sports. Mobility can be increased through various exercises and therapies. These exercises can also be done at home.
If the person affected also suffers from psychological complaints due to hypophosphatasia, contact with other affected people is very useful. In this way, information and tips for a pleasant everyday life can be exchanged and psychological complaints or depression can be avoided. Talking to friends and parents can also be helpful. However, a complete cure of this disease is not possible.