dihydropteridine reductase ( dhpr ) deficiency is a rare autosomal recessive inherited disease which affects the metabolism of tetrahydrobiopterin ( bh4 ) , causing hyperphenylalaninemia and neurotransmitter deficiency . delayed neurological syndromes due to hypomyelination in the central nervous system are recognized and can include parkinsonism . however , the clinical characteristics of parkinsonism and dopamine transporter ( dat ) imaging have not been fully documented . here , we report a case of levodopa - responsive parkinsonism with dhpr deficiency and demonstrate by means of dopamine transporter - single photon emission computed tomography ( dat - spect ) . a 16-year - old man was admitted to our hospital due to slowly progressive gait disturbance . he was found to have hyperphenylalaninemia on a routine guthrie test for newborn screening . he was diagnosed as having dhpr deficiency based on a bh4 loading test [ 2 , 3 ] . gene analysis revealed a compound heterozygous mutation of the qdpr gene ( g18c / s59x , both are new mutations ) [ 2 , 3 ] . at the age of 2 months , treatment was started with bh4 1520 mg / kg / day , levodopa 15 mg / kg / day , and 5-hydroxytryptophan ( 5-htp ) 15 mg to avoid intracerebral folate deficiency , folic acid was added when he was 15 years of age . neurological examinations revealed mental retardation , akinesia , rigidity of upper limbs , hand clumsiness , spastic paralysis , and clonus at the ankles . the mini - mental state score was 18/30 . at this time , the serum phenylalanine ( phe ) value was 906 nmol / ml ( normal , 42.675.5 nmol / ml ) . he was taking bh4 8.4 g / day , levodopa 700 mg / day , 5-htp 800 mg / day , entacapone 300 mg / day , folinic acid 15 mg / day , and levetiracetam 300 mg / day . brain magnetic resonance imaging ( mri ) showed high intensity areas in frontal and posterior deep white matter on fluid - attenuated inversion recovery ( flair ) ( fig . dopaminergic striatal innervation was evaluated as dopamine reuptake transporter density by means of spect and [ i]n--fluoropropyl-2-carbomethoxy-3-(4-iodophenyl ) tropane ( i - fp - cit ) . specific binding ratios were right 7.99 and left 8.13 ( normal , > 4.00 ) . his spastic gait improved with an antispasmogenic agent . levodopa - responsive dystonia is due to heterozygote mutations in the gtp cyclohydrolase 1 gene , where an endogenous synthesis of monoamines remains . gtp cyclohydrolase 1 , encoded by the gch1 gene , is an essential enzyme for dopamine production in nigrostriatal cells . loss - of - function mutations in gch1 result in severe reduction of dopamine synthesis in nigrostriatal cells and are the most common cause of dopa - responsive dystonia , a rare disease that classically presents in childhood with generalized dystonia and a dramatic long - lasting response to levodopa . the childhood - onset dystonia subtype has normal dat imaging ; however , dat imaging was reduced in the adult - onset parkinsonian subtype , indicating parkinson disease - like nigrostriatal dopaminergic denervation . gch 1 deficiency and consequent chronic dopamine deficiency with the adult - onset parkinsonian subtype might directly predispose to nigral cell death . our patient had no signs of monoamine deficiency under long - term replacement therapy despite the severe enzymatic deficiency and the long duration of the disease . this would suggest that a normal level of dopamine exhibits a protective role on the survival of nigral neurons . findings of parkinsonism in disorders of tetrahydrobiopterin metabolism on dat imaging have rarely been reported ( table 1 ) . evans et al .   reported a patient who had received a delayed diagnosis of phenylketonuria as an infant and developed motor fluctuations without dyskinesias . reported a patient who had no daily motor fluctuations or dyskinesias after long - term replacement treatment . our patient also had no daily motor fluctuations or dyskinesias after long - term replacement treatment . these findings suggest that early diagnosis and treatment with levodopa and 5-htp might lead to a favorable outcome . in addition to our case , 1 adult patient with the use of levodopa from the age of 3 months , despite the severe dhpr deficiency , exhibited no dyskinesia or dopaminergic cell loss , as suggested by normal positron emission tomography ( pet ) imaging of the dopamine transporter . although it is still under discussion whether the long - term use of levodopa is toxic for dopaminergic neurons , this observation and our case report suggest that early diagnosis and replacement therapy with levodopa and 5-htp might have protective effects on brain neurons during development .
we report a 16-year - old man with disorders of tetrahydrobiopterin metabolism due to dihydropteridine reductase ( dhpr ) deficiency . 
 he revealed moderate mental retardation , parkinsonism , and spastic paralysis with levodopa and 5-hydroxytryptophan ( 5-htp ) supplementation from the age of 2 months . 
 brain mri showed high intensity areas in bilateral frontal and posterior deep white matter on fluid - attenuated inversion recovery ( flair ) . 
 coronal flair image showed a high signal in bilateral pyramidal tracts . 
 single photon computed tomography ( spect ) imaging of the dopamine transporter was normal . 
 this imaging indicates no dopaminergic cell loss . 
 our patient had no motor fluctuations or dyskinesias . 
 early diagnosis and replacement treatment might lead to a favorable outcome .