Primary immune deficiency disorders (PIDs) are a heterogeneous group of disorders with symptoms overlapping with common diseases leading to delay in diagnosis. Many have autosomal recessive inheritance and present in early childhood. We report the phenotypic and molecular profile of PIDs from a tertiary care center in south India that caters to a population with high (∼35%) rate of consanguinity. The clinical data of a total of 101 unrelated patients diagnosed to have PIDs were collected and analyzed. Among our patients, hyper IgE syndrome (15.8%) followed by CVID (12.9%) were the two most common diagnoses of PIDs. Predominant antibody defects (28.7%) and well-defined syndromes (27.7%) were the two most common categories of PIDs, according to the 2017 IUIS phenotypic classification. Male gender was (1.4:1) slightly predominant. One-fourth had family history of undiagnosed early deaths and 17.8% had family history of PIDs. Parental consanguinity was present in 52.4%, significantly more than the population figure of 35%. Most common age at time of onset of symptoms was 1-3 months. Median time lapse between symptom onset and diagnosis was 18 months. Mortality rate in those admitted to ICU was significantly higher (p < 0.027) than general ICU mortality rate over the same period. Molecular analysis could be done in 26 patients, many of whom carried very rare or novel variants and some had >1 concurrent PIDs. Three patients with disseminated tuberculosis were found to have Immunodeficiency type 30 and 28. “Well-defined syndromes” and “Predominantly antibody deficiency” were the two most common classes according to the IUIS classification (2017). We conclude that PIDs are more commonly encountered than expected in the setting of high consanguinity, likely due to an excess of autosomal recessive inheritance. Very rare mutations were common when parents were consanguineous. Majority presented during early infancy. Mortality was higher than in general patients among those admitted to ICU.
