The database was originally an Access database that was used to record clinical information about the children notified to the PIND Study. It contains detailed data about the presenting symptoms and signs in the children with progressive intellectual and neurological deterioration (PIND) identified by the Study. It also records details of all the investigations that were carried out in these children, including those that were key to making the final diagnosis.

The Study commenced in May 1997. After an initially large number of notifications of prevalent cases in the first 20 months of the study, the number of notified cases of suspected PIND settled over the period 1999 to 2018 inclusive to between 146 and 230 per year - this notification rate continued to be relatively constant, despite the disruption caused by the COVID-19 pandemic. From 2019 until active surveillance ceased at the end of 2023 it was between 121 and 171 per year. After that 6 cases were notified, the last in April 2024. By April 2024, when the Study had been running for 27 years, 5222 children had been notified and the cases fell into the following groups. The 2540 'not cases' included those not meeting the PIND case definition, multiple notifications, reporting errors, and lack of information from the notifying paediatrician. There were 309 PIND children with no known diagnosis to explain their deterioration and there were 6 children with vCJD (4 definite and 2 probable).

2367 children with PIND had an underlying diagnosis to explain their deterioration, other than vCJD. The lifetime risk of having a disease causing PIND was calculated by taking the number of observed cases and dividing by the number of total births in the diagnosis period as suggested by Foss et al. The PIND Study diagnosis period was May 1997- April 2024. In the full years 1997 to 2023 inclusive there were 19,598,293 live births in the UK. This was taken as approximating to the PIND Study diagnosis period and these births were used to calculate the lifetime risk which was 0.1/1,000 live births. Demographics. Of the 2367 children who had diagnoses other than vCJD 1265 were male and 1102 were female. Data about ethnicity was available for 2185 of them. To compare the PIND Study UK data with the 2021 census of England and Wales24 the relevant ethnic groups were combined to produce the category Asian or Asian British. This Asian British group was made up of Indian (60), Pakistani (449), Bangladeshi (54), Asian (56), Chinese (6) making a total of 625. This was 28.6% of the 2185 for whom data about ethnicity was available. The distribution of the other ethnic groups was: White 1342 (61.4 %), Black 72 (3.3%), Mixed 67 (3.1%) and Other 77 (3.5%).

In the 2021 census in England and Wales the percentage of the population in the Asian, Asian British or Asian Welsh ethnic groups was 9.3%, White ethnic groups made up 81.7%, Black, Black British, Caribbean or African 4.0%, Mixed or Multiple ethnic groups 2.9% and Other ethnic groups 2.1%. The 2021 census data for England and Wales given above are not directly comparable to the PIND data which were collected from the whole UK between 1997 and 2023. However, the proportion of UK Asian British children in the PIND study at 28.6% is higher than the 9.3% of Asian, Asian British or Asian Welsh found in the census. Many of the diseases causing PIND in children are autosomal recessive so the relatively large proportion of Asian British in the PIND study group is not surprising - of the 393 children of Pakistani origin for whom the relevant information was available 93% had consanguineous parents. The rate was 71% in the Bangladeshi group, 28% in the Black group, 22% in the Indian and only 4% in the White ethnic group. Investigations - neuropathology and molecular genetics in the 2367 diagnosed children who did not have vCJD. Brain biopsies were carried out during life in 14 diagnosed children and in 13 they helped to make the diagnosis. These were: white matter disorders 4, Rasmussen encephalitis 3, mitochondrial diseases 2, astrocytoma 1, herpes simplex encephalitis 1, infantile Battens disease 1, multiple sclerosis 1. In 1312 children the results of molecular genetic investigations were available - in 864 cases (66% of the 1312) these provided the diagnosis or confirmed it. As time progressed an increasing proportion of cases were diagnosed by molecular genetic testing. The dates of testing were available for 573 of the 864 diagnostic results. In the first 5 years of the study (1997-2001 inclusive) molecular genetic testing contributed to the diagnosis in 32 children, in the last five years (2019-2023 inclusive) in 206 children. Once children had been diagnosed follow up by the PIND study ceased, however by the end of the Study in 2025 it was known that 1338 had died (confirmed via the NHS England Digital Spine25). Of these 39 had undergone post mortem investigations - all but one was carried out before 2010. In 25 of the 39 cases the post mortem investigations were helpful in making the diagnosis. This means that the diagnosis was made before death in 2367 - 25 = 2342 cases (99%). Of the 25 diagnostic post mortem studies one just had a liver biopsy (diagnosis: nonketotic hyperglycinaemia) another just had a bowel biopsy (diagnosis: Degos disease): in the other 23 brain tissue was available for neuropathological study - the diagnoses were: Alpers disease 5, other mitochondrial diseases 4, neurodegeneration with brain iron accumulation 4, white matter disorders 3, astrocytoma 1, Aicardi-Goutières syndrome 1, dentato-olivary dysplasia 1, GM1 gangliosidosis 1, Niemann-Pick type C 1, pontocerebellar hypoplasia 1, Rasmussen encephalitis 1. Post mortem immunocytochemical staining of the brain for abnormal prion protein was carried out in just two cases and was negative. Distribution of diseases causing PIND. The diagnosed group was made up of 2367 children with 238 different diseases other than vCJD - different genotypes were counted as separate diseases. The number of diseases increased with time as molecular genetic studies revealed more specific diagnoses. 136/238 (57%) were inborn errors of metabolism which occurred in 1820/2367 (77%) of the diagnosed children, showing that genetically determined (mainly autosomal recessive) diseases make a major contribution to PIND in UK children. The biggest group consisted of 581 leukodystrophies, the next of 364 mitochondrial diseases, followed by the 309 neuronal ceroid lipofuscinoses. There were 971 children (41% of the diagnosed group) with 42 different lysosomal diseases. Conclusion. The database is made up of a collection of case series can be identified searching for all the cases with specific diagnoses, giving unique information about the epidemiology and clinical features of more than 200 different neurodegenerative diseases of childhood.