PKU has been reported to co-existent with several immune disorders, including scleroderma, ulcerative colitis, Type 1 diabetes mellitus, autoimmune hepatitis Type 2, alopecia universalis, and Grave’s disease, but not JIA [
2]. JIA is a chronic idiopathic inflammatory disorder primarily involving joints. The peak incidence of JIA has been reported to occur at one to three years of age, with a preponderance of girls [
3]. The underlying mechanism of JIA is not fully understood. Interactions among genetic factors, immune mechanisms, and environmental exposures are thought to contribute. The pathophysiology of PKU co-existence with JIA is speculated as follows. Firstly, given the complexity and heterogeneity of autoimmune disorders, metabolites have been explored to discover diagnostic or prognostic biomarkers for these diseases. The accumulation of some abnormal metabolites like glycosaminoglycans, adiponectin and leptin may be involved in the development and progression of joint dysfunction in JIA [
4]. A recent metabolomics analysis revealed significantly higher ratios of both kynurenine/ tryptophan and phe/tyr and lower tryptophan levels in serum sample of JIA patients with high disease activity than those of clinically inactive patients [
5]. The researches proposed a hypothesis that chronic inflammation could alter tryptophan and tyrosine metabolism [
6]. Thus, PKU patients with chronic elevated Phe may be susceptible to JIA, in turn, co-existent JIA may have an effect on blood Phe. Finally, corticosteroid and methotrexate therapy for JIA may increase blood Phe concentration. MacDonald et al. reported that using corticosteroid was associated with increased blood Phe in 3/6 cases [
2]. In our study, Phe concentration had decreased continuously since the onset of treatment for JIA. A much-restricted diet may play a role in decreasing Phe concentration. Thus, the influence of corticosteroid therapy in patients with PKU needs more studies to confirm. We will continue to follow up the patient’s response to steroids.
If a patient with PKU develops arthralgia, a diagnosis of JIA should be considered. This is the first reported case of a girl with PKU co-existent with JIA. Continued follow up of this girl will help us gain further knowledge on treating this rare comorbidity. The pathophysiology of PKU co-existence with JIA needs to be further explored.