Segawa syndrome represents a very rare hereditary disorder of the nervous system that shows symptoms similar to Parkinson’s disease. The disorder belongs to the large group of dystonias, which are characterized by stiffening of the muscles. If the disease is correctly diagnosed, treatment is very simple and successful.
What is Segawa syndrome?
Segawa syndrome, as an extremely rare hereditary disorder of the nervous system, belongs to the large heterogeneous group of dystonias. Dystonia is characterized by stiffening of the muscles caused by a disturbance in the tone of the muscles. Involuntary contractions of the skeletal muscles take place. Convulsions and abnormal postures occur, which are maintained for a long time. However, the individual dystonias have different causes. Segawa syndrome is an idiopathic dystonia, i.e., muscle stiffness without an externally identifiable cause. It is now known that the disease is hereditary. The clinical picture of Segawa syndrome was first described by the Japanese neurologist Masaya Segawa in 1970. He also recognized that it is a disease in its own right. Because the syndrome has many similarities to Parkinson’s disease, it is still often confused with this disease and sometimes referred to as atypical Parkinson’s disease. However, Segawa syndrome has nothing to do with Parkinson’s disease. It is true that in both diseases there are disturbances in the dopamine metabolism. However, their causes are completely different. The disease is pronounced differently in individual patients and is therefore often not diagnosed immediately. For this reason, its frequency is not precisely known. It is believed that one per million people suffers from Segawa syndrome.
Causes
The cause of Segawa syndrome is thought to be a gene mutation on the long arm of chromosome 14. It is the GCH1 gene, which encodes the enzyme GTP cyclohydrolase. GTP cyclohydrolase is the rate-determining enzyme in the synthesis of tetrahydrobiopterin (BH4). Tetrahydrobiopterin is in turn responsible for the formation of dopamine. A mutation of the GCH1 gene can therefore lead to a deficiency of BH4 and thus of dopamine. The mutation is inherited in an autosomal dominant manner. However, the penetrance of the gene defect varies. In some patients, hardly any symptoms are observed, while in others they are severe. In some cases, autosomal recessive inheritance is suspected, but this is thought to be due to a different gene. This gene is located on chromosome 11 and is responsible for the coding of tyrosine hydroxylase. As a result of the described gene defects, there is a deficiency of dopamine. Thus, due to delayed synthesis, the neurotransmitter cannot be re-synthesized quickly enough after it is depleted. The stores for dopamine empty and are no longer available for muscle responses after a certain period of physical activity. Muscle stiffness results.
Symptoms, complaints, and signs
Segawa syndrome is initially manifested by gait disturbance, which becomes more pronounced as the day progresses. An inward position of the feet develops. This position can become so entrenched that further movement becomes impossible. It can happen that affected children go to school alone in the early morning and may even have to be picked up in a wheelchair in the afternoon because they can no longer walk. In the context of physical activity, dopamine stores are depleted in this disease and are not replenished quickly enough. In addition to inward rotation of the feet, Parkinson’s-like symptoms such as general muscle stiffness, lack of movement, tremors, or loss of postural reflexes may also occur. It has also been noted that more female than male patients are affected by Segawa syndrome. Usually, the first symptoms appear in the first decade of life at the age of four to eight years. However, in a few cases, symptoms do not begin until early adulthood.
Diagnosis and course of the disease
Segawa syndrome is actually very easy to diagnose. Based on the typical symptoms, the diagnosis can already be made. Typical of this disease is that the inability to move always occurs during the day after physical activity.After periods of rest or nighttime sleep, the symptoms gradually disappear. The cause for this is to be found in the too slow production of dopamine in the body. After correct diagnosis, Segawa syndrome is also the only dystonia that can be treated causally until the patient is free of symptoms. However, because this disorder is so rare, it is often not recognized by the examining physicians. Misdiagnosis occurs, often initiating a further course of suffering for some patients.
Complications
Segawa syndrome can cause severe complications in some circumstances. The typical gait disturbances occasionally lead to accidents and falls, which in turn cause fractures and injuries. In general, the condition causes severe physical discomfort. Symptoms such as tremors and muscle stiffness represent a considerable psychological burden for those affected in the long term. The result is mental disorders such as depression, anxiety disorders or inferiority complexes. Since it is mainly children who are affected, their parents often suffer as well. The need to care for one’s own children is associated with stress and anxiety, which can also develop into serious mental illnesses in the long term. Segawa syndrome therapy can also cause adverse events. For example, the drug L-DOPA, which is typically prescribed, can cause serious side effects. Typical symptoms include disturbances in movement, nausea and vomiting, urine discoloration and abdominal pain. Psychological disorders such as restlessness, anxiety disorders, and moodiness are also common. Sleep disturbances are also possible, as are digestive disorders, muscle stiffness, increased sweating and uncontrolled movements. In individual cases, side effects such as gastric bleeding, skin rashes and liver inflammation with bile stasis occur. Allergic reactions to the administered preparations cannot be ruled out either.
When should you see a doctor?
Segawa syndrome must always be examined and treated by a physician. There can be no self-healing in the process, as this is a hereditary disease and therefore cannot be treated causally, but only purely symptomatically. However, early diagnosis and treatment of the syndrome have a positive effect on the further course of the disease. A physician should be consulted for Segawa syndrome if the affected person suffers from a severe gait disorder, and this gait disorder usually worsens significantly if left untreated. Often, the affected person is then also dependent on a walking aid or even a wheelchair and can no longer cope with everyday life alone. Furthermore, trembling of the muscles also points to Segawa syndrome. If these symptoms occur, a doctor must be consulted in any case. Segawa syndrome is diagnosed by a general practitioner or an orthopedist, but further treatment must be carried out by a specialist. A complete cure cannot be obtained.
Treatment and therapy
After proper diagnosis, Segawa syndrome can be treated very well. The disease is not curable due to its hereditary condition, but with lifelong drug treatment, no symptoms appear. It is only necessary to compensate for the lack of dopamine production by substituting L-DOPA (levodopa). L-DOPA is a prodrug that is converted to dopamine in the brain. Dopamine itself cannot be administered because it cannot cross the blood–brain barrier. L-DOPA, however, can. It then forms dopamine in the brain, splitting off carbon dioxide, which maintains muscle movement.
Prevention
Prevention from Segawa syndrome is not possible. It is hereditary and a familial cluster is also not observed. After the first appearance of typical symptoms, only lifelong substitution with levodopa can provide symptom relief.
Follow-up
The affected person usually has few and also only very limited measures of direct aftercare available in Segawa syndrome. For this reason, the affected person should ideally see a physician at an early stage to prevent the occurrence of other complications and symptoms. Segawa syndrome cannot heal on its own. Since Segawa syndrome is a hereditary disease, it usually cannot be completely cured.For this reason, the affected person should have a genetic examination and counseling if he/she wishes to have children, in order to prevent the recurrence of the disease in the descendants. Some of the symptoms can be alleviated by taking various medications. The affected person should pay attention to a correct dosage and likewise to a regular intake of the medication in order to counteract the symptoms. Likewise, a doctor should be consulted first in case of severe side effects or if anything is unclear. The further course of this syndrome is strongly dependent on the exact manifestation of the disease, so that no general prediction can be made. Possibly, Segawa syndrome limits the patient’s life expectancy.
What you can do yourself
Segawa syndrome leads to a disturbed gait and sometimes falls in everyday life. That is why it is very important for those affected to take the prescribed medication correctly. Only with the appropriate medication can the symptoms be successfully avoided in the long term. The typical movement problems typically appear after physical activities and decrease after a rest or after a restful night. This is why there is a risk that sufferers recognize the problem too late. A medical diagnosis helps to analyze and treat the rare disorder. Unlike other dystonias, it can be successfully treated so that sufferers no longer experience symptoms. To minimize complications, patients should be careful when they notice the first signs of gait disorder. In this way, accidents and injuries can be avoided in time. Medication helps against the physical discomfort. Especially when the typical tremor occurs in combination with stiffening of the muscles, the psyche also suffers from the disease. This can lead to feelings of anxiety, complexes and depression. If children are affected, parents should inform themselves comprehensively in order to be able to help their offspring. This reduces the stress level and mental sequelae do not occur as quickly.
