EARLY ONSET PARKINSONISM: A NEW CLINICAL AND BIOCHEMICAL PHENOTYPE

A growing number of metabolic and degenerative diseases results in infantile parkinsonism. We report on a new clinical and biochemical phenotype so far not associated to any known aetiology. This 5-year-old child was born from non-consanguineous Italian parents after uneventful pregnancy and normal delivery. Psychomotor development was normal up to 4 months, when minimal tremor, upper limb dystonia and rigidity were detected. At 8 months neurological deterioration occurred associated with limb jerks, generalised hypokinesia/dystonia, and akinetic mutism. CSF examination disclosed low homovanillic acid (HVA) (185.5 nmol/L, r.v. 295-932), neopterin (7.8 nmol/L, r.v. 12-30), and biopterin (5.5 nmol/L, r.v. 15-40). TH and of GCH1 geneswere both normal. L-Dopa/Carbidopa treatment resulted in a partial clinical improvement. From the age of 4, diurnal fluctuations of symptoms and severe on/off phenomena required a progressive increase of L-Dopa/Carbidopa posology. Social interaction and language comprehension remained relatively spared. A further decline of HVA (77 nmol/L; r.v. 211-871) was found in CSF. SR, PTPS, GFRP genes sequences, and Array-CGH did not detect any alterations. Repeated Brain MRI and 1 H-MRS as well as an extensive neurogenetic and neurometabolic work-up were all normal. Dopamino-mimetic/synergic drugs (Selegilina, Tolcapone, Rotigotina, Pramipexole) proved to be ineffective