Navigating the complexity of managing coexisting inborn errors of metabolism and gender incongruence.

Clinical care and management of inborn errors of metabolism (IEM) are lifelong, complex, and resource-intensive for the healthcare team, patient, and families. A cohort of individuals with IEM who in addition have gender incongruence (GI) presents a unique challenge of patient care in current practices. Here, we discuss four patients with different IEM (phenylketonuria (PKU), 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD), ornithine transcarbamylase (OTC) deficiency that presented with GI either in their adolescence or adulthood. We review their IEM management and evolving expression of GI as we highlight the influence of various clinical and psychosocial stressors, including social acceptance and self-esteem. Significant research on the comorbidity between IEM and GI has not yet received attention in the literature. Here we aim to explore this underrepresented topic to encourage expansion of knowledge and how to navigate the complex management and support to individuals with IEM experiencing GI.