Patients with hEDS and MCAS very commonly report neuropsychiatric symptoms such as anxiety and depression.  Here we show two disorders, a primary immune disorder and a prevalent connective tissue disorder, are associated with chronic mast cell dysfunction and disruption of the epithelial borders, leading to multi-organ system pathology including central nervous system involvement.

We retrospectively studied 987 patients seen in our clinic, with a diagnosis of MCAS  from 2017 -2020. We identified 56 patients with mannose binding lectin deficiency, presenting with multi-organ system involvement, including mucocutaneous, articular and neurological features consistent with hEDS. We characterized their reported symptoms.

Among this cohort of patients with mannose binding lectin deficiency, MCAS and hEDS are common.  These observations implicate bi-directional influences of epithelial derived factors and mast cell activation in barrier function and tissue homeostasis which may guide further evaluation for patients presenting with neuropsychiatric complaints.