Infantile hypophosphatasia: a rare aetiology of recurrent pneumonia

We report a rare case of infantile hypophosphatasia associated with recurrent pneumonia, a condition with few similar cases documented globally. Clinical exome sequencing identified a heterozygous mutation in the alkaline phosphatase (ALPL) gene (c.69_74del; p.Glu23_Lys24del), the first such case reported in India and classified as 'likely pathogenic'. Its causality remains unproven due to limited evidence, including the absence of in vitro studies and pedigree analysis. Phenotypic variability may be influenced by factors such as incomplete penetrance, variable expressivity and environmental or epigenetic modifiers. This case highlights a rare but important cause of recurrent pneumonia in infants. Despite treatment, the child succumbed to severe pneumonia within 2 months. Clinicians should consider infantile hypophosphatasia in cases of recurrent pneumonia, motor delay, seizures, severe malnutrition and persistently low serum alkaline phosphatase. Further genetic and functional studies are needed to validate genotype-phenotype correlations and improve disease management.