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Background: Disorders of tetrahydrobiopterin metabolism represent a rare group of inherited neurotransmitter disorders which manifest mainly in infancy or childhood with developmental delay, neuroregression, epilepsy, movement disorders and autonomic symptoms.Methodology: A retrospective review of genetically con rmed cases of disorders of tetrahydrobiopterin metabolism over a period of three years (Jan 2018 to Jan 2021) was performed across two paediatric neurology centres from South India.Results: A total of nine patients(M:F=4:5) ful lled the eligibility criteria. The genetic variants detected include homozygous mutations in the QDPR(n=6), GCH1(n=2) and PTS(n=1) genes. The median age at onset of symptoms was 6-months(range 3-78 months), while that at diagnosis was 15-months (8-120 months) resulting in a median delay in diagnosis of 9-months. The main clinical manifestations included neuroregression (89%), developmental delay(78%), dystonia(78%) and seizures(55%). Management strategies included phenylalanine restricted diet, levodopa/carbidopa, 5-Hydroxytryphtophan, and folinic acid.Only, Patient-2 afforded and received BH4 supplementation at a sub-optimal dose later in the disease course. We had a median duration of follow up of 15 months (range 2-48 months). Though biochemical response has been marked, except for patients with GTPCH de ciency, only mild clinical improvement was noted with regards to developmental milestones, seizures or dystonia in others.Conclusion: Tetrahydrobiopterin de ciencies represent an rare yet potentially treatable cause for non-phenylketonuria hyperphenylalaninemia when diagnosed and treated early in life. Screening for disorders of biopterin metabolism in patients with hyperphenylalaninemia prevents delayed diagnosis. This study expands the genotype phenotype spectrum of patients with disorders of tetrahydrobiopterin metabolism from South India.

Introduction: Non-motor symptoms are an essential cause of comorbidity in generalized and focal dystonia. However, there are few studies on dystonia involving the craniofacial regions. Methods: We studied non-motor symptoms in patients with oromandibular dystonia (OMD) and Meige syndrome using a questionnaire, and validated instruments for depression, anxiety, REM behaviour disorder, restless leg syndrome, sleep quality, excessive daytime sleepiness, and self-esteem. The severity of dystonia and blepharospasm was also studied. Results: Nineteen patients with OMD were recruited into the study. Among patients with OMD, depression was seen in 63.6% ( n = 7), sleep impairment in 27.3% ( n = 3), excessive daytime sleepiness in 27.3% ( n = 3), and poor self- esteem in 18.2% ( n = 2) of the patients. Among patients with Meige syndrome, depression was seen in 37.5% ( n = 3), sleep impairment in 12.5% ( n = 1), excessive daytime sleepiness in 25% ( n = 2), low self-esteem in 25% ( n = 2) of the patients. Conclusion: This study highlights the significant frequency of depression and sleep disturbances in patients with idiopathic OMD and Meige syndrome.