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. Vascular cognitive impairment is a common yet preventable cause for dementia. It needs high degree of suspicion and appropriate designing of investigatory tools to confirm diagnosis, identify comorbidities, and ascertain the areas of impairment. Commonly DSM-IV criterion is applied for diagnosis and detailed clinical and neuropsychological examination for identifying the specific phenotype is used. Early diagnosis using the mandatory criteria will help in early initiation of disease modifying treatment strategies which can result in partial reversal of vascular changes and arrest of progression. Patients with young onset disease might require genetic characterization for designing more aggressive treatment.Discussion and Conclusion. Dementias as such carry poor course and prognosis resulting in severe Disability Adjusted Life Years (DALYs) for patients and caregivers. Therefore, it is mandatory to identify treatable and preventable causes so that man power loss can be reduced.