P1282 - Unveiling the Enigmatic Interplay: Malnutrition Masquerading as H63D Heterozygosity in Hereditary Hemochromatosis

Kingsley Ozongwu, MD¹, Kojo-Frimpong B. Awuah, MD², Matthew D. Simpson, MD², Tyrell Daniel, MD², Erasmus Mutabi, MD¹, Abdulahi Hassan, MD², Edmund Appiah-Kubi, MD², Chandan Dash, MBBS, MD³, Samuel Purkey, DO², Nabeeha Mohy-ud-din, MD^1
1Allegheny Health Network, Pittsburgh, PA; ²Allegheny General Hospital, Pittsburgh, PA; ³Allegheny Health Network Medicine Institute, Pittsburgh, PA

Introduction: Malnutrition is a rare cause of significant iron overload and can lead to a diagnostic dilemma when there is an overlap with less common HFE variants of hemochromatosis. While the classical C282Y mutation is well-recognized, the significance of less common variants, such as H63D, remains debated.1 Here, we present a case challenging the traditional paradigm of HFE mutations in HH, where malnutrition led to significant iron overload and elevated liver enzymes, overshadowing the diagnosis of H63D heterozygosity (HZ).

Case Description/Methods: A 52-year-old M with a history of anorexia nervosa (AN) with a BMI of 11.9 presented with nausea and generalized weakness. Labs revealed elevated liver enzymes, markedly elevated ferritin levels, and iron overload (Table 1). Despite therapeutic phlebotomy, his symptoms persisted. Genetic testing revealed H63D HZ. Liver biopsy demonstrated significantly increased iron in hepatocytes with kupffer cells and portal fibrosis. Salicylate, alcohol, and acetaminophen levels were negative, as were hepatitis A, B and C. In addition, liver ultrasound was largely unrevealing. Nutritional labs were notable for a vitamin A level of 15.3 ug/dL, and folate of 4.4 ng/mL with a suspected malnutrition state. After initiating enteral nutritional support, the patient's liver enzymes demonstrated a downtrend, highlighting the pivotal role of malnutrition in the manifestation of elevated liver enzymes rather than H63D HZ alone.

Discussion: This case challenges the conventional understanding of HFE mutations in HH. It shows how malnutrition, rather than H63D HZ, was the primary driver of iron overload and elevated liver enzymes with subsequent fall after nutritional optimization. Malnutrition compounded by severe anorexia nervosa, results in a heightened susceptibility to liver insults due to a lack of glycogen stores and reduced liver function reservoir.2 Moreover, specific risk factors for hyper-transaminasemia in AN, such as young age, low BMI, male sex, and the pure restrictive form of the disease, have been identified in studies, emphasizing the intricate interplay between malnutrition and hepatic dysfunction in this patient population.3 The presence of H63D HZ can mislead clinicians in the management of liver injury and this case highlights the importance of considering alternative explanations in patients with complex medical histories. Moreover highlights the critical role of nutritional support and vigilance in managing hepatic complications associated with AN.


Disclosures:


Kingsley Ozongwu, MD¹, Kojo-Frimpong B. Awuah, MD², Matthew D. Simpson, MD², Tyrell Daniel, MD², Erasmus Mutabi, MD¹, Abdulahi Hassan, MD², Edmund Appiah-Kubi, MD², Chandan Dash, MBBS, MD³, Samuel Purkey, DO², Nabeeha Mohy-ud-din, MD¹. P1282 - Unveiling the Enigmatic Interplay: Malnutrition Masquerading as H63D Heterozygosity in Hereditary Hemochromatosis, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.