Dopa responsive dystonia:diagnosis & treatment – by Dr. De León

This is a topic that is long over due since many of you who have Parkinsonism and dystonia may actually carry this diagnosis. At one time, early on in my clinical presentation, I and my neurologist also entertained this diagnosis as the etiology of my symptoms. DRD – Dopa Responsive Dystonia also known as Segawa syndrome in the recessive form.

This is a diagnosis that is often overlooked especially in childhood and early adulthood when most patients begin to exhibit dystonia as is the case for autosomal dominant DRD (DYT5a) caused by a GTP cyclohydrolase 1 deficiency. this deficiency can also be present in autosonal recessive DRD. Further, this enzyme is important in the production of BH4 (tetrahydrobiopterin) which is the substrate that converts phenelalanine to tyrosine. Tyrosine is the first step in conversion of dopamine.  bh4

In autosomal dominant disease symptoms begin early by age 6 often leading to a common misdiagnosis of cerebral palsy. (can also be the cause spastic paraplegia, early onset of generalized dystonia, and of early childhood parkinsonism very frequently).

One of the key characteristics of this DRD is gait dysfunction which worsen gradually with time but typically stabilizes by the third decade. Also more importantly is the diurnal variation in symptom presentation with symptoms being more pronounced in the evening after a full days activity. Improving with rest and sleep. Hence symptoms are usually significantly better in the morning. Plus the symptoms are exquisitely sensitive to dopa requiring very small doses (25-50mg) a day to control symptoms. Although some children and adolescents may develop dyskinesias with initial low doses of dopamine they always resolve with a lowering of dose and do not return with increasing doses again.

Unlike Parkinson’s, this is not considered a neurodegenerative disorder rather a metabolic abnormality. Typical symptoms include uncoordinated, clumsy gait something I had all my life. I lived my childhood with scraped knees and torn tights/leggins. Plus these patients are born with with club feet something I also had which required casting for my entire first year of life. So symptoms begin in lower extremities then migrate over time to involve upper extremities bilateral..again something I had. So of course this was high on list of suspects.

In general patients progress to develop generalized dystonia- I don’t have this. Furthermore, although some depression and sleep disturbances can occur with this syndrome, DRP patients do not exhibit autonomic dysfunction, intellectual, or sensory problems (common of PD) nor cerebellar disturbances (which are common of parkinson’s plus syndromes like MSA).

Rarely, these patients develop symptoms in adulthood instead in which case parkinsonism is the predominant feature rather than dystonia. unlike childhood onset these do not have a diurnal variation. But, on the plus side the movement disorder progresses extremely slow.

Diagnosis: ( I underwent genetic testing and had normal levels of these enzymes but did have an abnormality in another enzyme – which i have to find – of unclear etiology. Hence i am listed as rare cause of PD/dystonia at NIH)

  • as always a good history is a MUST! personal and family.
  • Genetic testing – as i did-look at DYT5 (dominant-GTPH1); look at tyrosine hydroxylase –TH deficiency (recessive)- this enzyme is the limiting factor in the pathway production of dopamine*; sepiapterin deficiency (both autosomal &dominant in children)
  • Mri’s of brain/dat scan normal-there is NORMAL uptake of dopamine
  • Spinal tap and look at CSF enzyme levels
  • blood and urine tests
  • sometimes muscle biopsies ( i almost had)

Although there is still much we don’t know about this illness especially since it has variation in presentation depending on age as well as enzyme involved and penetrance of gene (having the abnormality does not guaranty disease like many other neurological illnesses).- some even think there may be a DRD plus syndrome. Note_ so unless there are symptoms, there is no need to go fishing for genetic testing that might show abnormality that may never develop into anything.

Treatment is symptomatic with mainstay treatment being Levodopa! most patients do well with a dose between 200-400mg a day of levodopa.

In extremely rare cases there have been reports of patients having both DRD and PD- could I be one ? after a decade my dopamine dose remains low compared to my counterparts with same years of illness however, i also need many other dopamine agonists and MAO inhibitors to function i guess time will tell especially if NIH ever links other illnesses to my rare enzyme deficiency.

Find a Movement disorder specialist whom you can talk and listens to you and follow up routinely. Patients have done well with low dopamine for more than 2 decades. want to prevent contractions so PT and OT are crucial. this may also involve treatment with botox and centrally acting muscle relaxants like baclofen, dantrolene or baclofen pump. As well as rest to replenish dopamine.




All rights reserved Maria De Leon




Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: