Dopa-responsive dystonia (DRD) is a genetic movement disorder with unique clinical manifestations, synonymous with: genetic progressive dystonia with marked diurnal fluctuations (HPD) or Segawa disease, dopa-responsive fluctuating dystonia, juvenile genetic dystonia. HPD is a rare genetic disorder with dystonia or gait abnormalities as the first symptom in children or adolescents, which is clinically manifested by circadian fluctuations in symptoms and has a rapid and significant effect with low-dose dopa preparations. The disease is sporadic in half and autosomal dominant in half. 60% to 70% of DRD patients have mutations in the coding region of GCHⅠ at 14q32.1. 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 the dopaminergic neurons of the nigrostriatal system inevitably leads to Therefore, the deficiency of GCHⅠ in the nigrostriatal system leads to the decrease of tyrosine hydroxylase synthesis, which eventually leads to the decrease of dopamine level. Some scholars have tested the levels of hypericin and biotransferrin in the cerebrospinal fluid of DRD patients and found that both levels were 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 continuous administration of a small amount of exogenous dopa preparations can compensate for dopamine deficiency and relieve symptoms. Clinical manifestations of reactive dystonia are common in childhood, accounting for 10% of childhood dystonia, more females than males, with a male to female ratio of 1:4. The age of onset is between 1 and 12 years, generally between 4 and 8 years, but can be as early as infancy and as late as adulthood. The onset in infancy is rare and is often misdiagnosed as cerebral palsy or spastic paraplegia, sometimes manifesting only as late walking and easy falling. In adults, the onset of the disease is characterized by involuntary tremors and stiffness of the limbs, similar to Parkinson’s syndrome, slow movement, easy fatigue, high muscle tone, hyperactive tendon reflexes, and positive pathological signs. The initial symptoms are often horseshoe clubfoot and gait abnormalities due to lower limb hypotonia. Later, the disease worsens progressively and may present with stiffness of the extremities, bradykinesia and expressionless face. Half of the patients develop 8-10 Hz positional, intentional tremor (unlike the 4-5 Hz resting tremor of Parkinson’s disease), which is usually relatively stable in adulthood. Some patients with mild disease have difficulty walking and fatigue only in the afternoon, and have writing spasms when holding a pencil for a short time. In some children, ankle clonus and Babinski’s sign can be found on physical examination. 75% of children with dystonia have characteristic diurnal variation, i.e., dystonia is mild in the early morning when they first wake up, then gradually increases, and is most pronounced at dusk. This phenomenon becomes less pronounced with age, and generally progresses significantly within 20 years after the onset of the disease, tends to moderate in 20-30 years, and is almost stable by 40 years. The disease may improve slightly after daytime rest, but worsens with activity and exercise. In a few patients, the first symptom may be tremor. Dystonia may also be combined with bradykinesia, cogwheel-like muscle ankylosis, postural dysreflexia and other manifestations of Parkinson’s syndrome. Language and intelligence are often not involved. A dramatic and persistent response to small doses of levodopa is a distinctive clinical feature. All symptoms, including fatigue, dystonia, postural abnormalities, and tremor, disappear completely after dosing. In contrast, no dose increase is required for long-term levodopa administration, and no motor complications of levodopa occur. Diagnosis Based on children or adults with normal intelligence at the onset of the disease, with unexplained abnormal limb dystonia, tremor, and odd gait as the first symptoms, with morning lightness and evening heaviness as the main clinical features, especially those with a family history of genetic predisposition, and with efficacy to small doses of dopa preparations. Blood, urine, stool routine, usually normal, cerebrospinal fluid test, liver function test, EEG, evoked potentials, cranial CT, MRI and PET examination were normal. Treatment Small doses of dopa preparations have dramatic efficacy in DRD. Half of the patients saw the effect on the same day of medication, and the onset of effect usually does not exceed 7 days. Once the disease is suspected, immediate medication can be diagnostic treatment, levodopa 0.7-2.9mg/kg.d, divided into 3 doses, starting with small doses and adjusting the dosage according to the condition, generally when the function of the child is significantly improved, you can stop increasing the dosage; if 300mg/d is still ineffective, the disease can be ruled out. Adults can be treated with levodopa/benserazide (methyldopa) (levodopa 0.7-2.9mg/kg/day, carbidopa 0.2-0.7mg/kg/day, gradually increasing as needed). It can be used continuously for a long time without increasing the dose, and there are no side effects such as switching on and off (sudden hyperactivity of patients is “on” and then muscle tonic movement is “off”) and reduced efficacy of the drug. If the drug is discontinued, the symptoms will reappear. If the medication is stopped, the symptoms will reappear.