Diffuse interstitial lung disease revealing prolidase deficiency in a newborn: a case report and review of the literature

Abstract Background Prolidase deficiency (PD) is a rare autosomal recessive disorder typically characterized by skin lesions, recurrent infections, and developmental delay. Diffuse interstitial lung disease (ILD) is an uncommon manifestation and may be under-recognized. Case presentation We report the case of a 1-month-old white French boy, presenting with recurrent bronchiolitis, associated with a macular rash and persistent fever. Chest computed tomography (CT) revealed ILD with subpleural cysts, bronchiectasis, and bilateral ground-glass opacities (GGO). Whole genome sequencing identified a homozygous variant in the PEPD (Peptidase D) gene, classified as likely pathogenic (ACMG class 4). Biochemical analysis confirmed PD. In addition to the neonatal presentation, the patient exhibited elevated serum IL-18 levels and an increased type I interferon signature, an immunological combination not previously reported in PD, although its pathogenic significance remains uncertain. Conclusions This case expands the phenotypic spectrum of PD by describing a neonatal presentation with severe diffuse ILD and a previously unreported association of elevated IL-18 and type I interferon activation. PD should be considered in infants with unexplained ILD, and urinary iminodipeptiduria together with PEPD analysis can facilitate early diagnosis.