Macrophagic myofasciitis associated with transferrin receptor 2 and solute carrier family 40 member 1 variants and iron dysregulation: a case report.

backgroundMacrophagic myofasciitis (MMF) is a rare inflammatory muscle disease linked to the long-term persistence of aluminum-based adjuvants in macrophages. Its clinical spectrum includes fatigue, myalgia, and cognitive impairment, and genetic susceptibility has been suggested. To our knowledge, this is the first reported case suggesting an association between MMF, mild yet clinically relevant iron dysregulation, and variants in key iron regulatory genes, including transferrin receptor 2 (TFR2) and solute carrier family 40 member 1 (SLC40A1), also known as ferroportin. CASE PRESENTATION: We report the case of a 55-year-old white French woman of Breton maternal origin and predominantly Northwestern European/Celtic ancestry, presenting with chronic fatigue, musculoskeletal pain, and cognitive impairment. Muscle biopsy confirmed the diagnosis of MMF with aluminum deposition in macrophages. Iron indices had remained within the normal range for many years. After menopause, she gradually developed increasing ferritin levels, intermittent elevations in liver enzymes, and transferrin saturation values occasionally approaching or exceeding the upper normal limit, despite regular voluntary blood donations. These episodes showed a recurrent temporal pattern, with increases in ferritin and transferrin saturation coinciding with elevations in hepatic enzymes and clinical worsening. Both biological parameters and symptoms improved following blood donations and later after dietary iron restriction. Direct-to-consumer ancestry genetic testing with secondary raw data analysis identified homozygous variants in TFR2 and heterozygous variants in SLC40A1. Repeated blood donations led to a marked decrease in ferritin and transferrin saturation, normalization of liver enzymes, and transient improvement in several symptoms, but were poorly tolerated, causing prolonged fatigue and episodic dyspnea. After discontinuation of blood donations, progressive dietary iron restriction reduced transferrin saturation and normalized liver enzymes without further phlebotomy, while ferritin gradually increased toward the upper reference range.

conclusionsThis case highlights a possible contribution of genetic susceptibility to MMF, involving variants affecting iron regulation and macrophage function. It raises the hypothesis of a gene-environment interaction in which altered iron handling could contribute to both an enhanced hepatic response to modest iron loading and prolonged persistence of aluminum adjuvants within macrophages. Further studies are needed to better define the potential role of iron-related genes, particularly TFR2 and SLC40A1, in MMF susceptibility and to explore whether individualized preventive approaches might be relevant in genetically predisposed individuals.