S4139 Copper Conundrum: Nutritional Deficiencies Masquerading as Other Metabolic Diseases

Introduction: Nutritional deficiencies are a recognized complication following bariatric surgery, yet they can resemble the clinical presentation of other metabolic diseases. This case illustrates diagnostic complexities that arise when micronutrient deficiencies present with overlapping clinical and biochemical characteristics of other metabolic disorders. Case Description: A 52-year-old woman with a pertinent history of myasthenia gravis, tardive dyskinesia, and Roux-en-Y gastric bypass (RYGB) presented with encephalopathy, anasarca, ascites, and hyperammonemia concerning for cirrhosis despite a lack of radiographic evidence. Workup revealed low serum ceruloplasmin (9 mg/dL), low serum copper (36 mcg/dL), and decreased 24-hour urinary copper (<5 mcg/24 hr). Liver biopsy revealed F3 fibrosis, iron deposits in hepatocytes and Kupffer cells, and positive copper staining. Genetic testing revealed hereditary hemochromatosis protein heterozygosity for H63D and ATP7B with no mutations. Evaluation for ornithine-transcarbamylase (OTC) deficiency revealed low urinary orotic acid, elevated ornithine, normal glutamine, and elevated citrulline. The patient’s mental status improved with lactulose, and her lab values improved with ongoing aggressive nutritional interventions. Discussion: The differential diagnoses in this case included Wilson’s disease (WD) and OTC deficiency, both of which can present with hepatic dysfunction and encephalopathy. However, the diagnosis was complicated by paradoxical findings. Though Wilson’s disease presents with low serum copper and ceruloplasmin with hepatic copper retention, low urinary copper and negative genetic testing was inconsistent with the diagnosis. Similarly, hyperammonemia with low urinary orotic acid, normal glutamine, and elevated citrulline argued against a primary urea cycle disorder. The patient’s history of RYGB, known to impair copper absorption, offered a unifying explanation. Nutritional deficiencies can impair synthesis of functional ceruloplasmin, which is needed to excrete copper into the circulation. As a result, copper accumulates in the liver and leads to decreased serum copper and ceruloplasmin levels, mimicking WD. Additionally, the absence of functional ceruloplasmin can impair hepatic iron metabolism, leading to iron accumulation in the liver. This case highlights how nutritional deficiencies can masquerade as metabolic diseases. A high index of suspicion and a thorough dietary, surgical, and clinical history are essential to accurate diagnosis and management.