Abstract

Abstract Background Rare disorders comprise of ~ 7500 different conditions affecting multiple systems. Diagnosis of rare diseases is complex due to dearth of specialized medical professionals, testing labs and limited therapeutic options. There is scarcity of data on the prevalence of rare diseases in different populations. India being home to a large population comprising of 4600 population groups, of which several thousand are endogamous, is likely to have a high burden of rare diseases. The present study provides a retrospective overview of a cohort of patients with rare genetic diseases identified at a tertiary genetic test centre in India. Results Overall, 3294 patients with 305 rare diseases were identified in the present study cohort. These were categorized into 14 disease groups based on the major organ/ organ system affected. Highest number of rare diseases (D = 149/305, 48.9%) were identified in the neuromuscular and neurodevelopmental (NMND) group followed by inborn errors of metabolism (IEM) (D = 47/305; 15.4%). Majority patients in the present cohort ( N = 1992, 61%) were diagnosed under IEM group, of which Gaucher disease constituted maximum cases ( N = 224, 11.2%). Under the NMND group, Duchenne muscular dystrophy ( N = 291/885, 32.9%), trinucleotide repeat expansion disorders ( N = 242/885; 27.3%) and spinal muscular atrophy ( N = 141/885, 15.9%) were the most common. Majority cases of β-thalassemia ( N = 120/149, 80.5%) and cystic fibrosis ( N = 74/75, 98.7%) under the haematological and pulmonary groups were observed, respectively. Founder variants were identified for Tay-Sachs disease and mucopolysaccharidosis IVA diseases. Recurrent variants for Gaucher disease ( GBA :c.1448T > C), β-thalassemia ( HBB :c.92.+5G > C), non-syndromic hearing loss ( GJB2 :c.71G > A), albinism ( TYR :c.832 C > T), congenital adrenal hyperplasia ( CYP21A2 :c.29–13 C > G) and progressive pseudo rheumatoid dysplasia ( CCN6 :c.298T > A) were observed in the present study. Conclusion The present retrospective study of rare disease patients diagnosed at a tertiary genetic test centre provides first insight into the distribution of rare genetic diseases across the country. This information will likely aid in drafting future health policies, including newborn screening programs, development of target specific panel for affordable diagnosis of rare diseases and eventually build a platform for devising novel treatment strategies for rare diseases.