Delayed diagnosis of doparesponsive dystonia in two siblings. Initial diagnostic confusion with cerebral palsy or spastic diplegia existed in 16 patients. Doparesponsive dystonia drd is a rare but highly treatable form of genetic dystonia. There may be insufficient awareness of dopa responsive dystonia drd, which has a characteristic diurnal variation of symptoms. Dystonia is a movement disorder that causes involuntary contractions of your muscles. These contractions result in twisting and repetitive movements.
Dopa responsive dystonia with diurnal fluctuation discussion diminished central synthesis of dopamine is the presumed neurochemical deficit in drd. This form of dystonia is called doparesponsive dystonia because the signs and symptoms typically improve with sustained use of a medication known. The symptoms were relatively mild in the morning and became severe in the late afternoon or evening. Phenotype of five patients with doparesponsive dystonia. Nov 01, 20 the estimated european prevalence of dopa responsive dystonia drd ranges from 11,000,0001200,000. Doparesponsive dystonia drd is a specific form of dystonia that most commonly affects children, and often can be well managed with levodopa. Late onset doparesponsive dystonia with tremor, gait. The first was thought to have hysteria and the second hereditary spastic paraparesis. Apr 30, 2015 doparesponsive dystonia drd is diagnosed based on the signs and symptoms present, results of laboratory tests sometimes including genetic testing, and response to therapy with levodopa. Doparesponsive dystonia drd encompasses a group of clinically and genetically heterogeneous disorders that typically manifest as limbonset, diurnally fluctuating dystonia and exhibit a robust and sustained response to levodopa treatment. The term drd is applied to several disorders characterized by stiff movement, abnormal gait, and sometimes abnormal mouth movements. A very rare neurometabolic disorder characterized by a spectrum of symptoms ranging from those seen in doparesponsive dystonia drd to progressive.
Drd symptoms might be similar to those of earlyonset generalized dystonia. Mar 25, 2019 dopamine responsive dystonia drd, also known as dopa responsive dystonia or as hereditary progressive dystonia with diurnal variation hpd, is an inherited dystonia typically presenting in the first decade of life although it may present in the second to early third decades, or even later. Doparesponsive dystonia drd is an inherited type of dystonia that typically begins during childhood but may begin in adolescence or adulthood. Dopa responsive dystonia or, drd, is a hereditary form of dystonia. Dopa responsive dystonia drd is a condition characterized by the onset of dystonia in early childhood with dramatic and sustained response to treatment with levodopa. Wholegenome sequencing of patient dna can facilitate diagnosis of a disease, but its potential for guiding treatment has been underrealized. Segawa syndrome nord national organization for rare. Segawa syndrome nord national organization for rare disorders. Classification of doparesponsive dystonia a patients. Dopa responsive dystonia drd encompasses a group of clinically and genetically heterogeneous disorders that typically manifest as limbonset, diurnally fluctuating dystonia. Dopa responsive dystonia often begins during childhood, between ages six and sixteen, and usually involves an abnormal, stiff way of walking with the foot bent or turned, although it may also affect the arms and torso. Dopa responsive dystonia drd is a childhoodonset dystonic disorder, characteristic symptoms include dystonia typically absent in the morning or after rest but worsening during the day and with exertion. Dopa responsive dystonia drd is a childhoodonset dystonic disorder, characteristic symptoms include dystonia typically absent in the morning or after rest but worsening during the day and. Doparesponsive dystonia with depigmentation of the substantia nigra and formation of lewy bodies.
Dyt5a occurs more frequently than autosomal recessive drd dyt5b. Doparesponsive dystonia dystonia medical research foundation. Main side effects dry mouth, blurred vision, constipation, decreased concentration, and hallucinations. The most common form of doparesponsive dystonia drd is autosomal dominant drd caused by a mutation in the gch1 gene. Depending on the specific type of drd, specific symptoms can vary. Jun 17, 2016 classification of doparesponsive dystonia a patients perspective. Several recently published articles discuss the clinical and genetic heterogeneity of drd phenotypes in relation to the. These disorders include tyrosine hydroxylase deficiency autosomal recessive dopa responsive dystonia, aromatic lamino acid decarboxylase deficiency, sepiapterin reductase deficiency. The estimated european prevalence of dopa responsive dystonia drd ranges from 11,000,0001200,000. We present an interesting case of recurrent dystonic crises in dopa responsive dystonia drd likely induced by excessive consumption of aspartamecontaining products, in. It can be considered a form of childhood parkinsons disease.
Woongwoo lee beom seok jeon 0 department of neurology, seoul national university hospital, seoul, korea dopa responsive dystonia drd has a classic presentation of childhood or adolescentonset dystonia, mild parkinsonism, marked diurnal fluctuations, improvement with sleep or rest, and a dramatic and sustained response to low doses of l dopa. Combination with tricyclic antidepressants may increase side effects. This has a strong practical value as acute presentations to the emergency department can be avoided in these susceptible individuals. Delayed diagnosis of doparesponsive dystonia in two siblings rahul jain, b haskar shukla and medha mittal from department of pediatrics, chacha nehru bal chikitsalaya, geeta colony, delhi, india background. Doparesponsive dystonia with depigmentation of the substantia nigra and formation of lewy bodies jan e. Dystonia can affect just one muscle, a group of muscles or all of your muscles. Combination with tricyclic antidepressants may increase side. In particular, earlyonset generalised ppd with spasmodic dysphonia is a characteristic phenotype caused by dyt6 mutations class iv 27. Pdf misdiagnosis in children with dopa responsive dystonia.
Dopamine responsive dystonia drd also known as segawa syndrome ss, is a genetic movement disorder which usually manifests itself during early childhood at around ages 58 years variable start age characteristic symptoms are increased muscle tone dystonia. Several patients benefited from anticholinergic medications and a few from carbamazepine. A group of movement disorders that respond to levodopa. We examined 106 members of a family affected with dopa responsive dystonia drd, a subset of idiopathic dystonia. Doparesponsive dystonia drd is a disorder that typ ically presents in childhood with dystonia. Response to levodopa treatment in doparesponsive dystonia. Clinicians should recognize movement disorder to be a presenting feature of a. The clinical spectrum can range from subtle neurologic signs and symptoms e.
Dopamineresponsive dystonia an overview sciencedirect. The features of this condition range from mild to severe. Doparesponsive dystonia drd, also known as segawas disease, is another form of dystonia that can have a genetic cause. Its symptoms may be similar to those of early onset generalized dystonia. Segawa1 postulated a disturbance in sleep regulation of neurotransmitters related to l dopa. For all other comments, please send your remarks via contact. This group includes inherited forms that are characterized by progressive difficulty walking. Dopa responsive dystonia may show autosomal recessive or dominant inheritance.
Woongwoo lee beom seok jeon 0 department of neurology, seoul national university hospital, seoul, korea dopa responsive dystonia drd has a classic presentation of childhood or adolescentonset dystonia, mild parkinsonism, marked diurnal fluctuations, improvement with sleep or rest, and a dramatic and sustained response to low doses of l dopa without motor fluctuations or dyskinesias. We have reported postmortem brain data in one asymtomatic and two symptomatic cases with gtp cyclohydrolase 1deficient dopa responsive dystonia, in whom substantially decreased levels, not only of tetrahydrobiopterin but also of neopterin, were confirmed in the brain furukawa et al. Doparesponsive dystonia drd describes a group of neurometabolic disorders. Parkinsonism in gtp cyclohydrolase 1deficient dopa. Physicians should distinguish choreoathetotic cp from dopamine. Functional analysis of single nucleotide substitutions within the 5 untranslated gch1 region ioanna a. Wholegenome sequencing for optimized patient management. In most cases, dystonia begins in the lower limbs and spreads to the upper limbs over time. Doparesponsive dystonia and earlyonset parkinsons disease. Levodopa is an amino acid that is converted to dopamine. Genetic dystonias that are known to run in families include. Jun 15, 2011 wholegenome sequencing of patient dna can facilitate diagnosis of a disease, but its potential for guiding treatment has been underrealized.
Dopa responsive dystonia drd is a treatable neurological condition which can present with a variety of symptoms ranging from dystonia, spastic paraparesis, and proximal weakness to parkinsonism. Doparesponsive dystonia drd was first recognized by segawa et al. T in children even in the absence of frank ataxia or telangiectasias. Dystonias fact sheet national institute of neurological. This form of dystonia is called doparesponsive dystonia because the signs and symptoms typically improve with sustained use of a medication known as l dopa. Primary torsion dystonia which may include childhood and adult onset, generalized and focal symptoms dopa responsive dystonias myoclonus dystonia. Only comments seeking to improve the quality and accuracy of information on the orphanet website are accepted. We interrogated the complete genome sequences of a 14yearold fraternal twin pair diagnosed with dopa 3,4dihydroxyphenylalanine responsive dystonia. Fortyseven of these patients had hereditary disease. Doparesponsive dystonia drd is an umbrella term used to describe specific dystonia disorders that respond to a medication called levodopa, which is a synthetic form of a brain chemical called dopamine. Dystonic crises in doparesponsive dystonia induced by. Dopamineresponsive dystonia an overview sciencedirect topics. May 22, 2014 doparesponsive dystonia drd was first recognized by segawa et al.
Dystonia nord national organization for rare disorders. We report observations on the treatment of 66 patients with presumed dopa responsive dystonia drd. Guidelines for the diagnosis and treatment of primary. The profound and sustained benefit of levodopa to a child with doparesponsive dystonia drd provides a compelling reason to be aware of drd.
Twenty members had lesser dystonic signs and symptoms suggestive of a diagnosis of dystonia. Dopa responsive dystonia due to gtp cyclohydrolase 1. Dopa responsive dystonia is a rare condition whose symptoms are easily treated with lowdose dopaminergic therapy. Segawa1 postulated a disturbance in sleep regulation of neurotransmitters related to l dopa metabolism to. Our report adds further features to the phenotype of drd caused by gchl gene mutations. Special points trihexyphenidyl is a secondline treatment, because levodopa reverses the bio. Examples of dystonia that is responsive to dopaminergic drugs include the following.
Gtpch1deficient drd genetic and rare diseases information. We have reported postmortem brain data in one asymtomatic and two symptomatic cases with gtp cyclohydrolase 1deficient dopa responsive dystonia, in whom. Doparesponsive dystonia with depigmentation of the. Dystonic crises in doparesponsive dystonia induced by energy. Expanding the spectrum of doparesponsive dystonia drd and. The 2 patients improved markedly by l dopa treatment. The most commonly identified form is termed, dopa responsive dystonia, which is a dominantly inherited condition caused by mutations in the gtp cyclohydrolase 1 gene gtpch1. Dopa responsive dystonia drd, a childhoodonset or adolescentonset form of dystonia with marked diurnal fluctuation and an excellent response to levodopa, is among the bestdescribed forms of monogenic dystonia. Dopa responsive dystonia drd is generally an autosomal dominant disorder manifest as dystonia and particularly in older patients, as parkinsonism. Dopamine is a brain chemical that serves as a neurotransmitter and is deficient in individuals with drd. Neurotransmitters are naturally produced molecules. Doparesponsive dystonia may respond to more than ldopa. Four dystonia plus syndromes have been characterized genetically.
Symptoms can include tremors, voice problems or a dragging foot. We present an interesting case of recurrent dystonic crises in dopa responsive dystonia drd likely induced by excessive consumption of aspartamecontaining products, in particular sugarfree energy drinks. Dopa responsive dystonia with diurnal fluctuation segawas. Two children are reported in whom the diagnosis of drd was missed. Lena elisabeth hjermind, phd, md,1,2 lis gitte johannsen. Another common form of drd is caused by a mutation in the recessively inherited tyrosine hydroxylase gene hth. Deep brain stimulation dbs may be recommended for some individuals with dystonia, especially when medications do not sufficiently alleviate symptoms or the side effects are too severe.
Several recently published articles discuss the clinical and genetic heterogeneity of drd phenotypes in. Dopa responsive dystonia was first described in 1976 by segawa. We interrogated the complete genome sequences of a 14yearold fraternal twin pair diagnosed with dopa 3,4dihydroxyphenylalanine responsive dystonia drd. Doparesponsive dystonia genetics home reference nih. In those with dopamine responsive dystonia, symptoms typically dramatically improve with lowdose 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.
In many patients onset is characterised by an abnormal, stifflegged manner of walking, with upward bending of the sole of the foot, or turning of the foot outward at the ankle and a tendency to walk on the toe. Doparesponsive dystonia drd has a classic presentation of childhood or adolescentonset dystonia, mild parkinsonism, marked diurnal. It is characterized by progressive difficulty with walking. Gtp cyclohydrolase 1deficient dopa responsive dystonia. Few patients may present with signs of parkinsonism that may include bradykinesia, rigidity, balancing difficulties, and postural instability. Dopa responsive dystonia was first described by segawa et al. These abnormalities are often severe, especially in the afternoon. Dopa responsive dystonia drd is a general term for a few disorders in which generalized dystonia and parkinsonism are present and often dramatically respond to treatment with levodopa.
If drd is suspected, a therapeutic trial with low doses of levodopa remains the most practical approach to the diagnosis. Dopa responsive dystonia with diurnal fluctuation segawa. Dopa responsive dystonia is characterized by progressive disabling dystonia. A family history of dystonia or parkinson disease is common.
This form of drd is usually characterized by childhoodonset dystonia that may be associated with parkinsonism at an older age. Autosomal recessive dopa responsive dystonia orphanet. Dopa responsive dystonia in children mink 281 main drug interactions may decrease efficacy of antipsychotic medications. More than 140 mutations in the gch1 gene have been found to cause dopa responsive dystonia. Dystonia is a state of continuous contraction of groups of agonist and antagonist muscles resulting in a sustained abnormal posture. Doparesponsive dystonia is a disorder that involves involuntary muscle contractions, tremors, and other uncontrolled movements dystonia. Usual medical and dietary advice in the treatment of.
They described 2 female cousins who showed gait disturbance with dystonia at ages 4 and 6. This condition is characterized by a pattern of involuntary muscle contractions dystonia, tremors, and other uncontrolled movements and usually responds to treatment with a medication called l dopa. Classification of doparesponsive dystonia a patients perspective. Doparesponsive dystonia, segawa syndrome, levodopa. Dyt5a occurs more frequently than autosomal recessive drd. It often responds very well to regular doses of levodopa a synthetic form of the brain chemical. We describe and provide video for twin patients with a rare form of dopa responsive dystonia due to sepiapterin reductase deficiency. Clinical spectrum of doparesponsive dystonia and related.
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