A Case of Aceruloplasminemia Which Was Not Wilson Disease

Abstract

Case: A 58 year old woman presented with 5+ years of fatigue and joint pain as well as recent short term memory concerns. She was evaluated for Lyme disease and was found to have mild anemia with elevated iron and persistently elevated ferritin as high as 2100 ng/ml. An unrelated cardiac scan had the incidental finding of hepatic iron accumulation. No fibrosis was noted on MRI. Liver biopsy was significant for 3-4+ hemochromatosis with sinusoidal dilation and congestion. Labs showed aceruloplasminemia with low urine and serum copper. Eye exam was negative for Kayser Fleischer rings but did show retinal iron deposits and early macular degeneration not supporting Wilson disease. Later genetic testing for CP (ceruloplasmin) gene showed heterozygosity for sequence variant c.2342A>C, predicted to cause amino acid substitution p.Lys781Thr.

Conclusion: She is currently awaiting MRI to evaluate possible CNS disease in the setting of aceruloplasminemia but was delayed due to significant COVID-19 risk. Otherwise, she is tolerating deferasirox well.

Significance: Our patient had a complex path to diagnosis given that low ceruloplasmin is commonly associated with Wilson disease. However, ceruloplasmin is also a key component in regulating ferric iron binding to transferrin and maintaining copper and iron homeostasis. This case was an exemplar of interdisciplinary diagnosis. Clinical evidence of anemia, ophthalmologic findings, and subjective cognitive dysfunction combined with histology and genetic results contributed to accurate characterization of aceruloplasminemia related hemochromatosis rather than Wilson’s disease. Genetic analysis revealed CP gene c.2342A>C (p.Lys781Thr), a novel mutation not reported elsewhere to our knowledge. Given her heterozygous status for the mutation, further investigation is needed. More importantly for our patient, recognition and treatment at this stage could reduce morbidity from neurodegeneration, pancreatic, and hepatic disease.