Dopamine-responsive dystonia also known as Segawa syndrome , is a geneticmovement disorder which usually manifests itself during early childhood at around ages 5–8 years. Characteristic symptoms are increased muscle tone and Parkinsonian features, typically absent in the morning or after rest but worsening during the day and with exertion. Children with dopamine-responsive dystonia are often misdiagnosed as having cerebral palsy. The disorder responds well to treatment with levodopa.
Signs and symptoms
The disease typically starts in one limb, typically one leg. Progressive dystonia results in clubfoot and tiptoe walking. The symptoms can spread to all four limbs around age 18, after which progression slows and eventually symptoms reach a plateau. There can be regression in developmental milestones and failure to thrive in the absence of treatment. In addition, dopamine-responsive dystonia is typically characterized by signs of parkinsonism that may be relatively subtle. Such signs may include slowness of movement, tremors, stiffness and resistance to movement, balance difficulties, and postural instability. Approximately 25 percent also have abnormally exaggerated reflex responses, particularly in the legs. These symptoms can result in a presentation that is similar in appearance to that of Parkinson's disease. Many patients experience improvement with sleep, are relatively free of symptoms in the morning, and develop increasingly severe symptoms as the day progresses. Accordingly, this disorder has sometimes been referred to as "progressive hereditary dystonia with diurnal fluctuations." Yet some people with dopamine-responsive dystonia do not experience such diurnal fluctuations, causing many researchers to prefer other disease terms. ;Other symptoms - footwear
excessive wear at toes, but little wear on heels, thus replacement of shoes every college term/semester.
;Other symptoms - handwriting
near normal handwriting at infants/kindergarten years.
and autosomal recessive forms of the disease have been reported. Mutations in several genes have been shown to cause dopamine-responsive dystonia. The precursor of the neurotransmitterdopamine, L-dopa, is synthesised from tyrosine by the enzymetyrosine hydroxylase and utilises tetrahydrobiopterin as a cofactor. A mutation in the geneGCH1, which encodes the enzyme GTP cyclohydrolase I, disrupts the production of BH4, decreasing dopamine levels. This results in autosomal-dominant dopamine-responsive dystonia. Mutations in the genes for tyrosine hydroxylase and sepiapterin reductase result in autosomal-recessive forms of the disease. When the latter enzyme is affected, the condition tends to be more severe. The activity of dopaminergic neurons in the nigrostriatal pathway normally peaks during the morning and also decreases with age until after age 20, which explains why the symptoms worsen during the course of the day and with increasing age until the third decade of life.
typically referral by GP to specialist Neurological Hospital e.g. National Hospital in London.
very hard to diagnose as condition is dynamic w.r.t. time-of-day AND dynamic w.r.t. age of patient.
correct diagnosis only made by a consultant neurologist with a complete 24-hour day-cycle observation at a hospital, i.e., morning ->noon->afternoon->evening->late-night->sleep->morning.
patient with suspected dopamine-responsive dystonia required to walk in around hospital in front of Neuro'-consultant at selected daytime intervals to observe worsening walking pattern coincident with increased muscle tension in limbs.
throughout the day, reducing leg-gait, thus shoe heels catching one another.
diurnal affect of condition: morning, lunch, afternoon, evening, bedtime.
muscle tension in thighs/arms: morning, lunch, afternoon, evening, bedtime.
;Diagnosis - additional
lack of self-esteem at school/college/university -> eating disorders in youth thus weight gains.
lack of energy during late-daytime -> compensate by over-eating.
Treatment
In those with dopamine-responsive dystonia, symptoms typically dramatically improve with low-dose administration of levodopa, which is a biochemically significant metabolite of the amino acid phenylalanine, as well as a biological precursor of the catecholamine dopamine, a neurotransmitter. Low-dose L-dopa usually results in near-complete or total reversal of all associated symptoms for these patients. In addition, the effectiveness of such therapy is typically long term, without the complications that often occur for those with Parkinson's disease who undergo L-dopa treatment. Thus, most experts indicate that this disorder is most appropriately known as dopa-responsive dystonia. No data are available on mortality associated with dopamine-responsive dystonia, but patients surviving beyond the fifth decade with treatment have been reported. However, in severe, early autosomal recessive forms of the disease, patients have been known to pass away during childhood. Girls seem to be somewhat more commonly affected. The disease less commonly begins during puberty or after age 20, and very rarely, cases in older adults have been reported. Due to commonly being misdiagnosed, it is common for the disease to remain untreated. When left untreated, patients often need Achilles' tendon surgery by the age of 21. They will also struggle with walking, an ability that will degrade throughout the day. Power napping can provide temporary relief in untreated patients. It also impairs development into adulthood, reduces balance, and reduces calf muscle development. Socially, it can result in depression, lack of social skills, and inability to find employment.
Epidemiology
This condition is very rare, only affecting one in two million people. It is more common in females than in males. There are several hundred cases in the United States, 25 known cases in the United Kingdom, and less than that in Australia and New Zealand.
Research
Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders.
History
The disease is named after Dr. Masaya Segawa, who provided an early clinical description.
