Dope-reactivated dystonia (DRD), also known as Segawa disease, is a rare genetic disorder that occurs in children or adolescents with dystonia or gait abnormalities as the first symptom. It is characterized clinically by diurnal fluctuations in symptoms and by the rapid and pronounced effect of small doses of dopa preparations. it was first described by Segawa et al. in 1976.
The disease is sporadic in half and partially autosomal dominant or recessive. It is believed that a deficiency of GCHⅠ, an isoenzyme of GTP cyclizing hydrolase, leading to a decrease in dopamine synthesis is the main cause of DRD (Nagatsu 1998).
Foreign scholars found that 60%-70% of DRD patients have mutations in the coding region of GCHⅠ at 14q32. Since GCHⅠ is an important rate-limiting enzyme for the synthesis of tetrahydrobiopterin, which is an essential cofactor for catecholamine biosynthesis, the deficiency of GCHⅠ in dopaminergic neurons of the nigrostriatal system must lead to a decrease in tyrosine hydroxylase synthesis and eventually to Therefore, the deficiency of GCHⅠ in the nigrostriatal system must lead to a decrease in tyrosine hydroxylase synthesis and ultimately to a decrease in dopamine levels.
The levels of hypericin and biotransferrin and neotransferrin in the cerebrospinal fluid of DRD patients have been measured and found to be lower than normal. Positron emission tomography (PET) examination revealed normal striatal 18F-dopa uptake, suggesting that dopamine decarboxylase and dopamine receptors are normal in this disease, so continued administration of small amounts of exogenous dopa preparations can compensate for dopamine deficiency and relieve symptoms.
Clinical manifestations
1, DRD onset of age 1 to 12 years old, accounting for 10% of children with dystonia, a few patients can be as late as 50 to 60 years old. The incidence of female > male, male: female = 1:4.
In children, the first symptom is abnormal muscle tone of one lower limb, and the child has a strange gait, stiffness of the lower limb, unstable gait, and clubfoot. Sometimes, the child only shows delay in learning to walk and falls easily, but as the disease progresses, the abnormal muscle tone affects other limbs, even the head and neck and the body’s central axis, and spastic slanting neck and twisting spasm appear. Children may have limb tremor, muscle tonicity and positive automatic Babinske’s sign, but language and intelligence are generally not involved.
In adults, involuntary tremor and stiffness of the limbs resemble Parkinson’s syndrome. The patient’s movement is slow, easily fatigued, with increased limb tone, hyperactive tendon reflexes, and positive pathological signs. 75% of patients have circadian fluctuations in symptoms, which are significantly reduced or even disappear in the morning or after rest, and worsen in the afternoon or after exertion.
4. Most of the patients have progressive disease course, and those who have not been treated will eventually be unable to take care of themselves.
The diagnosis is mainly based on clinical manifestations and responsiveness to small doses of dopa preparations. In children or adults, DRD should be highly suspected if the first symptom is abnormal limb tone, tremor and strange gait of unknown origin, and the main clinical features are light in the morning and heavy in the evening, especially if there is a family history of DRD.
Suspected patients given oral small dose of dopa preparation, most of the symptoms in 1 to 3 days relief, if not effective, the dose can be increased appropriately, (Torbjoerna, 1991), carbidopa/levodopa dose to 25/100 (containing levodopa 100mg and carbidopa 25mg), 3 times / d, still not effective, the diagnosis of DRD can be ruled out.
Differential diagnosis
DRD should be differentiated from cerebral palsy, juvenile Parkinson’s disease, torsional spasm, hepatomegaly, spastic paraplegia, etc.
1, cerebral palsy: often characterized by abnormally high muscle tone and spasticity, but often accompanied by mental retardation, convulsions and mood disorders, with no fluctuation of symptoms and no response to dopa preparations.
Juvenile Parkinson’s disease: rarely occurs in children under 8 years of age, PET examination shows decreased uptake of 18F-dopa, long-term application of dopa preparations need to gradually increase the dose, and prone to side effects such as isokinetic and end-dose deterioration.
3, hepatomegaly: often accompanied by liver damage and intellectual and psychiatric abnormalities, K-F ring can be seen in the cornea.
4, Very few patients have cool initial symptoms and signs like spastic paraplegia, and dramatic reactivity of small doses of dopa may be the most important point of differentiation.
Dietary modifications
Papaya and pineapple porridge: take 50g each of net papaya and pineapple and l00g of japonica rice. add japonica rice, papaya and pineapple into a pot with appropriate amount of water and cook together to make porridge.
Oilseed rape tofu: take 250g of net oilseed rape leaves, 200g of tofu, appropriate amount of salt, monosodium glutamate, green onion and veggie oil. Wash the rape leaves, tofu cut square dice, put oil in the pot, heat up and put in the onion stir-fry, then put in the rape leaves, stir-fry the aroma when adding water to boil, put in the tofu dice, a little burn, add salt, MSG, burn to taste.
Cheerios honey paste: take 500g of Cheerios, honey 1000mg. remove impurities and wash the Cheerios, use white gauze to twist out the juice, put it into the pot. Put the honey into the pot of carrion juice and mix well, put on a low fire and boil until thickened, leave the fire, cool and set aside in the altar.
Patients can eat more food containing magnesium, fatty acids, vitamin E and protease, there is no special contraindication.
Treatment
Prevention is more important for those with genetic background. Preventive measures include avoidance of consanguineous marriage, introduction of genetic counseling, carrier genetic testing and prenatal diagnosis and selective abortion to prevent the birth of affected children. Early diagnosis and early treatment to enhance clinical care is important to improve the quality of life of patients.
Small doses of dopa preparations have dramatic therapeutic effects on DRD. About half of the patients see the effect on the same day of taking the drug, and the onset of action usually does not exceed 7 days, therefore, once the disease is suspected, the drug is given immediately as a diagnostic treatment.
The recommended dose abroad is levodopa/benserazide (methyldopa) 0, 125 to 0, 25g/d in 2 to 3 doses. In China, the dosage of levodopa/benserazide is generally 62,5~187,5mg/d. There are reports of 15 years of continuous use without any side effects, but if the drug is stopped, the symptoms will reappear.