A Novel Manifestation of Prolidase Deficiency in a Toddler Diagnosed With Very‐early‐onset Crohn Disease

lume 69, N association with the W (VEO-CD) in unexpected finding of prolidase deficiency (PD) by whole-exome sequencing (WES). CD is a chronic granulomatous inflammatory bowel disorder that may affect the entire gastrointestinal tract and extraintestinal sites (1). Although the average age of diagnosis of pediatric inflammatory bowel disease (IBD) is 10 to 12 years, the fastest rates of rise in new diagnoses have been in children younger than 5 years (2), which represents the subset of VEO-IBD. Patients with VEO-IBD account for 15% of all pediatric IBD cases and can have a worse prognosis, as they may not respond to conventional therapies. WES has played a vital role in identifying monogenic defect in a subset of VEO-IBD (3). One such genetic defect is PD, an autosomal recessive disorder of proline and hydroxyproline metabolism. PD leads to impaired collagen synthesis causing delayed wound healing. PD is usually associated with cutaneous ulcers, dysmorphic facies, skeletal deformities, splenomegaly, mental retardation, and recurrent infections. Incidence of PD is extremely rare (1–2 per 1,000,000 individuals); thus far, only 93 cases have been reported in the literature, usually in consanguineous or genetically restricted populations (4). This rare combination of VEO-CD and PD has only been described in the literature once (5) but should be considered in cases of VEO-IBD complicated by recalcitrant skin ulcers and findings not typical of CD.