Clinical spectrum and diagnostic delay in rare diseases of children: Experience from a tertiary care centre in India

Background and objectives Rare diseases, though individually uncommon, collectively pose a significant public health burden. In India, diagnostic delays and limited therapeutic availability continue to hinder optimal management. This study aimed to describe the clinico-epidemiological profile of paediatric patients with rare diseases and to evaluate diagnostic delays and access to therapy in a tertiary-care setting. Methods This hospital-based, ambispective observational study was conducted from May 2020 to August 2021, during which 180 child patients with rare diseases were enrolled. Disorders were classified according to the International Classification of Diseases, 10th Revision (ICD-10). Demographic, clinical, and diagnostic details were recorded, including age at presentation, age at diagnosis, and diagnostic delay. Data on access to genetic testing and orphan drug therapy were also analysed. Results Of the 180 children, 16.7% (n=30) had ultra-rare diseases. Forty-eight diagnostic categories were identified, with the most frequent being neurological and neuromuscular disorders (n=49, 26.7%), haematological disorders (n=34, 18.9%), lysosomal storage disorders, and congenital malformations and chromosomal anomalies. The median (IQR) diagnostic delay was 3.0 (0.5-5.0) y. Genetic testing was performed in 48% (n=86) of patients, with a diagnostic yield of 59% among those tested. Only 12.8% (n=23) received orphan drug therapy, primarily due to procurement delays and non-formulary status. Interpretation and conclusions The broad diagnostic spectrum of paediatric rare diseases in our cohort, with predominance of neurological and neuromuscular disorders, reflects their clinical heterogeneity. The relatively high diagnostic yield and uptake of genetic testing in our cohort reflect improving diagnostic capabilities in India. However, access to therapy remains limited, highlighting persistent gaps in care delivery.