165 Prolidase deficiency in an infant with an incidental finding of methaemoglobinaemia

Background A 4-week-old infant presented to hospital with diarrhea and vomiting. An initial diagnosis of cow’s milk allergy was made and he was discharged with extensively hydrolysed formula. However the infant was readmitted within a week with ongoing symptoms and associated metabolic acidosis. He was suspected to have sepsis and treated with intravenous antibiotics. However, he deteriorated further with worsening metabolic acidosis despite treatment. Methaemoglobinaemia was then identified and he was treated with methylene blue and transferred to HDU for further management. Objectives Consider Methaemoglobinaemia as a differential diagnosis in infants with unexplained metabolic acidosis. Raise awareness on Prolidase deficiency – a rare genetic condition affecting 1 in 1 million of worldwide population. Methods Literature search on Ovid using Medline/Embase was undertaken. Results Conclusions Further investigations results of Imidopeptiduria and rapid exome sequencing confirmed diagnosis of Prolidase deficiency (PD) in this infant. PD is a rare autosomal recessive genetic condition caused by mutations in PEPD gene, which codes for Prolidase, an enzyme involved in the final stage of the degradation of collagen and other proline containing proteins including dietary proteins. PD affects approximately 1 in 1 million worldwide. The symptoms of PD include dysmorphic features, skin lesions, recurrent infections, hepatosplenomegaly and intellectual disability. In this case, the child had symptoms of diarrhoea, likely secondary to PD. As the diarrhoea was persistent, he then developed methaemoglobinaemia as a result. Initial methaemoglobin was 48% which subsequently improved to 3% following 3 doses of methylene blue with good clinical response. Further investigations excluded Systemic lupus erythematosus and Crohn’s disease, which have been reported as associated with PD. The infant’s recovery was supported with parental nutrition and discharged home with ongoing follow up with Paediatric metabolic specialists. Management of PD is mainly supportive with consideration of use of co-factors that can improve collagen stability, suppression of collagenase and topical application of ointments containing L-proline. Enzyme replacement is also being actively researched. This case illustrates the importance of prompt recognition and treatment of methaemoglobinaemia in infants with unexplained metabolic acidosis. It also highlights awareness of PD, which although, is extremely rare, can be diagnosed through metabolic screening tests and genetic testing, thereby leading to earlier supportive management.