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Neurology India
Medknow Publications on behalf of the Neurological Society of India
ISSN: 0028-3886 EISSN: 1998-4022
Vol. 51, Num. 2, 2003, pp. 252-253

Neurology India, Vol. 51, No. 2, April-June, 2003, pp. 252-253

Case Report

Patient with limb girdle dystrophy presenting with dopa-responsive dystonia - A case report

R. Verma, S. Misra, N. N. Singh, D. Kishore

Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi.

Rajesh Verma
Lecturer, Department of Neurology, King George's Medical College, Lucknow.

Accepted on 18.03.2002.

Code Number: ni03078


Dopa-responsive dystonias are rare. We report a 14-year-old male who was diagnosed as a case of limb girdle dystrophy and had features suggestive of dopa-responsive dystonia.

Key Words: Dopa-responsive dystonia, Limb girdle dystrophy.

Dopa-responsive dystonia (DRD) accounts for about 5% of all dystonias in children. It typically presents with dystonia of the lower limbs affecting gait or occasionally as a focal dystonia.1 Parkinsonian features have been reported in patients as the disease progresses. We report a case of limb girdle dystrophy that presented with features suggestive of DRD.


A 14-year-old boy presented with complaints of tremors all over the body for 3-and-a-half years, difficulty in initiation and slowness in execution of movements, abnormal posturing and stiffness, mainly in the lower limbs for 2-and-a-half years. All these features had diurnal fluctuations. He was well in the morning and could perform his routine activities but in the evening he developed abnormal posturing, mainly of the lower limbs. This was accompanied by rest tremors. The patient also complained of difficulty in climbing stairs as well as progressive thinning and weakness in proximal musculature of both the upper and lower limbs for the last five years. Selegeline therapy resulted in partial improvement in the tremors.

On examination, he had cogwheel type rigidity in all the four limbs. There was grade 3-4 quadriparesis, power in the distal muscles was better than the proximal muscles. The knee and ankle jerks were depressed. Sensory system examination did not reveal any abnormality. Serum CPK was raised (560 IU/Lt). CT scan did not reveal any abnormality. Nerve conduction studies over median, ulnar, peroneal and sural nerves bilaterally were within the normal range. Electromyographic studies revealed small-duration, low-amplitude, myopathic potentials with absence of spontaneous activity and complete interference pattern. Muscle biopsy studies showed a few foci of necrosis of muscle fibers and occasional areas showed regenerative fibers, increased sarcoplasmic basophilia, and large vesicular nuclei with prominent nucleoli. Findings were suggestive of muscle dystrophy.

Following therapy with low dosage of levo-dopa with Trihexyphenidyl (2 mg twice a day), the patient showed dramatic improvement in the extrapyramidal signs.


DRD accounts for about 5% of all dystonias in children. It typically presents with dystonia of the lower limbs affecting the gait or occasionally as a focal dystonia.2 Parkinsonian features have been reported in patients as the disease progresses. The patients show a marked diurnal fluctuation in their symptoms, which get worse after exertion, fatigue or in the latter part of the day. The disorder is more common in females. Typical diurnal variations whereby the patient is better in the mornings and worse in the evenings is seen in only 30% of cases.3 Also, older family members may present with parkinsonism and not dystonia. The phenotype of this condition is expanding and a dopa challenge should be done in all children labeled as dystonic cerebral palsy as they may turn out to DRD.4

The first biochemical clue to the role of dopamine in DRD came with the discovery of a decrease in the level of tetrahydrobiopterin in CSF along with decreased urinary levels of homovanelic acid, a metabolite of dopamine.5

DRD dystonia shows autosomal dominant inheritance with reduced penetrance and sex-linked expression with female preponderance. The gene is located on chromosome 14. Ichinose et al (1994) identified point mutations in the gene for GTP cyclohydrolase.6 This is a rate-limiting enzyme involved in the formation of the tetrahydrobiopterin cofactor of dopamine biosynthesis. It should be borne in mind that other defects in the dopamine pathway can also present with dopa-responsive dystonia, for example tyrosine hydroxylase gene mutation on chromosome 21 inherited as an autosomal recessive condition presents with dopa-responsive dystonia, seizures and mental retardation.6

According to Jeon et al,7 in DRD, the absence of degenerative nigral cell loss underlies the remarkable L-dopa response. He proposed the concept of DRD as a syndrome defined as selective nigrostriatal dopamine deficiency caused by genetic defects in dopamine synthesis without degenerative cell loss. He further proposed the term DRD-plus as inherited metabolic disorders which have symptomatic features of DRD.7 Green PE et al have reported 4 patients with DRD who had asymmetric dystonia and limb atrophy on the more affected side.8 Chaudhary et al have reported a case of DRD with vitiligo.9

We could not locate any in which there was an association of DRD and limb girdle dystrophy. It may be that there is some correlation between limb girdle dystrophy and dopa-responsive dystonia due to the fact that DRD also occurs due to mutation on the tyrosine gene on chromosome 21 while some types of limb girdle dystrophy have involvement of chromosome 21. Further genetic studies are required.


1. Nygaard TG, Snow BJ, Fahn S, et al. Dopamine responsive dystonia; Clinical characteristics and definition. In: Segawa M, editor. Hereditary progressive dystonia with marked diurnal fluctuation. Canfoth, UK: Panthenion; 1993. pp. 21-35.
2. Nygaard TG, Trugman JM, De Yebenes JG, et al. Dopa-responsive dystonia. The spectrum of clinical manifestations in a large North American family. Neurology 1990;40:66-9.
3. Segawa M, Hosaka A, Miyagawa F, et al. Hereditary progressive dystonia with marked diurnal fluctuation. Adv Neurology 1976;14:215-33.
4. Nygaard TG, Waran SP, Levine RA, et al. Dopa responsive dystonia simulating cerebral palsy. Pediatr Neurol 1994;11: 236-40.
5. Williams AC, Eldridge R, Levine RA, et al. Low CSF hydroxylase cofactor (Tetrahydrobiopterin) levels in inherited dystonia. Lancet 1979;2:214-8.
6. Ichinose H, Ohye T, Takashahi E, et al. Hereditary progressive dystonia with marked diurnal fluctuations caused by mutations in the GTP cyclohydrolase 1 gene. Nat Genet 1994;8:236-42.
7. Jeon BS. Dopa responsive dystonia a syndrome of selective nigrostriatal dopaminergic deficiency. Published erratum appears in J Korean Med Sci 1997;12:480.
8. Green PE, Bressman SB, Ford B, et al. Parkinsonism, dystonia and hemiatrophy. Mov Disord 2000;15:537-41.
9. Chaudhary N, Mani J, Rawat S, Mulye R, Shah P. Dopa responsive dystonia in a girl with vitiligo. Indian Pediatr 1998;35: 663-5.

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