Epidemiology of progressive intellectual and neurological deterioration in UK children

Abstract

Aim: To study the neurodegenerative diseases that cause progressive intellectual and neurological deterioration (PIND) in children in the UK. Method: This active prospective epidemiological study asked UK paediatricians to notify all childhood cases of PIND via the British Paediatric Surveillance Unit. Clinical data were obtained using a questionnaire or via a site visit. An independent PIND study Expert Group classified the cases. Results: Between May 1997 and April 2024 (27 years), 2373 children with PIND were identified who had an underlying diagnosis to explain their deterioration. There were six cases of variant Creutzfeldt–Jakob disease plus 2367 children (1265 males, 1102 females) with other diseases. The lifetime risk of having a diagnosed disease causing PIND was 0.1 in 1000 live births. Asian British children made up 28.6% of the 2183 cases with known ethnicity. Excluding variant Creutzfeldt–Jakob disease, diagnosed children had 259 diseases, identified before death in 99% of children (only 39 were known to have had postmortems). Increasingly, diagnosis was made using genetic studies. Sixty-one per cent (157 of 259) of the diseases were inborn errors of metabolism, affecting 78% of diagnosed children. There were 43 lysosomal diseases. Interpretation: This unique epidemiological study of many rare childhood neurodegenerative diseases provides valuable practical information about the presentation, clinical features, and inheritance of these complex disorders.