NeurometPlus

Incidence

This type of autosomal dominant childhood dystonia has been reported more than 200 cases in many countries. The disease is more common in females.

Clinical Characteristics

Clinically the disease looks like idiopathic torsion dystonia but the onset is frequently earlier from infancy to early adolescence. Dystonic spasms are first manifest in one of both lower extremities leading to gait abnormality which may be misinterpreted as cerebral palsy. Later, extrapyramidal signs spread to the trunk, arms, and neck. Tremor and other parkinsonian features are added especially when the patient reaches adulthood. Two third of cases have diurnal fluctuations as a characteristic feature (Segawa disease). Dystonic posture and rigidity tends to appear in late afternoon and is much less pronounced in the morning and after sleep. CT scan and MRI is normal. Dopa-responsive dystonia appears to lead to a dysfunction or deficit of dopamine within the nigrostriatal dopaminergic system. The hallmark of the disease is its rapid and remarkable response to small amounts of Levodopa. The penetration however is not 100 %, so assay of enzyme activity will be needed. Symptoms of this condition usually start around six years of age. Very rarely there are some neonatal symptoms such as spasticity with hyperreflexia and extension plantar response. Also, in infancy is very rare to see this condition. The symptoms of dystonia are usually present in childhood and adolescence to adulthood. Parkinsonian syndrome may be present in childhood and adolescent but usually present in adulthood. As previously reported, diurnal variation of symptoms may be present in two thirds. Spasticity, pes echinovarus, hyperreflexia and extensor plantar response may be present, especially extended Babinski-like toe in childhood. Muscle tone is increased at all ages including the neonatal period. Rest tremor may be present in adolescence or adulthood. Bradykinesia may be present since infancy. Pyramidal and extrapyramidal signs may be present since the neonatal period. Postural instability can be present since infancy. Developmental delay may be seen in infancy. Rigidity is always present at all ages. Oculogyric crisis can be seen in infancy and childhood. Diagnosis relies on the analysis of neurotransmitters and their metabolites in CSF, urine and plasma. Organic acids and aminoacids are normal. There is great decrease concentration of tetrahydrobiopterine (BH4) and neopterine in CSF. Diagnosis is made by measuring enzymes in lymphoblasts or fibroblasts. Four different mutation has been described in this condition so molecular DNA studies should be able to detect individuals who are at risk. Routine laboratory testing is normal. There is decreased homovanillic acid (HVA) in CSF at all ages. 5-hydroxyindoleacetic acid (5HIAA) in CSF may be normal or decreased. Neopterine and tetrahydrobiopterine (BH4) in CSF are decreased at all ages. Levodopa combined with carbidopa is very effective in doses as low as 25 mg. twice a day but treatment should be maintained indefinitely.

Precipitants

No. However remember that two third of cases have diurnal fluctuations as a characteristic feature (Segawa disease).

Provocation Tests

A trial with L-dopa may show dramatic clinical improvement in the first 1-2 days of treatment.

Diagnostic Procedures

EB-F,W. Diagnosis relies on the analysis of neurotransmitters and their metabolites in CSF, urine and plasma. There is great decrease concentration of tetrahydrobiopterine (BH4) and neopterine in CSF. Routine laboratory testing is normal. There is decreased homovanillic acid (HVA) in CSF at all ages. 5-hydroxyindoleacetic acid (5HIAA) in CSF may be normal or decreased. Neopterine and tetrahydrobiopterine (BH4) in CSF are decreased at all ages. Diagnosis is made by measuring enzymes in lymphoblasts or fibroblasts.