Pregnancy-desiring older woman with FH-deficient uterine leiomyoma: Case report and literature review

Fumarate hydratase (FH)-deficient uterine leiomyoma (FHDUL) is a rare type of uterine fibroid associated with FH gene mutation. In 36-year-old pregnancy-desiring older woman, the cumulative oxidative stress damage and FH functional defects may synergistically accelerate the process of metabolic abnormalities. Metabolic reprogramming triggered by reduced FH activity not only leads to the accumulation of 2-succinyl cysteine (2SC) and the stabilization of hypoxia-inducible factors but also exacerbates age-related mitochondrial dysfunction, further compromising DNA repair ability. mechanisms significantly increase the risk of tumor development. Genetic detection is the diagnostic gold standard, and the combination of immunohistochemistry in the absence of FH protein and increased expression of 2SC can assist in diagnosis. For such elderly patients, fibroidectomy is the first choice if reproduction is needed, but special attention should be given to age-related ovarian dysfunction. After surgery, fertility assessment should be performed as soon as possible and assisted reproductive technology intervention should be considered; if there is no need for fertility, then hysterectomy is recommended. For elderly patients with germline FH gene mutations, multidisciplinary collaborative management must be strengthened, with a focus on screening for hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC)-associated renal cell carcinoma, and follow-up is recommended to be shortened considering the aging factor interval. At present, the international guidelines for the diagnosis and treatment of FHDUL are still imperfect, and the clinical data for elderly patients are especially limited. The diagnosis and treatment experience of a 36-year-old FHDUL patient with a familial genetic tendency provides important information for the clinical management of this special population.