O01 Inborn errors of metabolism - Solving the puzzle of prolidase deficiency

Abstract

Abstract Inborn errors of metabolism (IEM) may present with ­distinctive cutaneous manifestations as part of a multisystem phenotype. Diagnosis is a multidisciplinary affair, made difficult by their rarity and complex genetic architectures. Knowledge of molecular mechanisms provides hope for targeted therapies, but unmet needs remain in the treatment of skin disease. Prolidase deficiency (OMIM #170100) is a rare IEM characterised by impaired collagen recycling, recalcitrant lower limb ulceration and massive imidodipeptiduria. The cases of two siblings born to related parents are reported, presenting initially in childhood with hydroa vacciniforme-like photosensitivity. Following a decade-long journey, the diagnosis of prolidase deficiency was eventually made. Pitfalls including the limitations of conventional diagnostic modalities and whole genome sequencing are examined, as well as the effects of chronic skin changes and associated disability on quality of life in childhood and adolescence. Therapeutic options, possible connections to hydroa vacciniforme, and prospects for translational research are reviewed. A rational approach to the clinical and genetic diagnosis of IEM in the paediatric dermatology clinic is proposed.