Clinical Presentation of a Patient With Hemochromatosis After Bariatric Surgery With HFE (H63D) Mutation.

Hereditary hemochromatosis (HH) is a genetic disorder characterized by excessive intestinal iron absorption, most associated with HFE C282Y homozygosity. In contrast, H63D homozygosity is considered a low-penetrance genotype that rarely leads to clinically significant iron overload. Bariatric surgery, particularly sleeve gastrectomy, may predispose patients to iron deficiency through reduced gastric acid and altered absorption. We report an unusual case of iron overload physiology in a patient with H63D homozygosity following sleeve gastrectomy, highlighting the diagnostic challenges posed by metabolic comorbidities and altered post-surgical physiology. A 51-year-old man with class III obesity, dyslipidemia, hypertension, vitiligo, obstructive sleep apnea, and a history of sleeve gastrectomy presented for weight management. Despite an initial 97-lb postoperative weight loss, he experienced significant weight regain along with fatigue, decreased libido, and skin darkening. Laboratory evaluation demonstrated hypogonadotropic hypogonadism, elevated serum iron (229 µg/dL), and transferrin saturation (60%) with normal ferritin (118 ng/mL). FibroScan revealed F3 fibrosis and grade 3 steatosis, consistent with advanced metabolic dysfunction-associated steatotic liver disease. Genetic testing confirmed H63D homozygosity. Pituitary MRI was unremarkable. The patient had increased alcohol intake prior to surgery, followed by a substantial reduction to moderate weekend use. The patient's iron overload was notable given his low-penetrance genotype and prior bariatric procedure. This case illustrates the complex interplay between genetic predisposition, metabolic disease, alcohol use, and altered gastrointestinal anatomy in shaping iron indices. It emphasizes the clinical relevance of transferrin saturation and comprehensive metabolic assessment. Clinicians should maintain vigilance for atypical presentations of HH in individuals with metabolic dysfunction or prior bariatric surgery.